OBJECTIVE

Reliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast- and slow-growing GAs present different gene expression profiles and reliable biomarkers for tumor growth potential could be identified, focusing on the specific role of epithelial-mesenchymal transition (EMT).

METHODS

Eight GAs selected for RNA sequencing were equally divided into fast- and slow-growing group by the tumor volume doubling time (TVDT) median (27.75 months). Data were analyzed by tophat2, cufflinks and cummeRbund pipeline. 40 genes were selected for RT-qPCR validation in 20 GAs based on significance, fold-change and pathway analyses. The effect of silencing MTDH (metadherin) and EMCN (endomucin) on in vitro migration of human adenoma cells was evaluated.

RESULTS

350 genes were significantly differentially expressed (282 genes upregulated and 68 downregulated in the fast group, P-adjusted <0.05). Among 40 selected genes, 11 showed associations with TVDT (-0.669<R<-0.46, P < 0.05). These were PCDH18, UNC5D, EMCN, MYO1B, GPM6A and six EMT-related genes (SPAG9, SKIL, <em>MTDH</em>, HOOK1, CNOT6L and PRKACB). <em>MTDH</em>, but not EMCN, demonstrated involvement in cell migration and association with EMT markers.

CONCLUSIONS

Fast- and slow-growing GAs present different gene expression profiles, and genes related to EMT have higher expression in fast-growing tumors. In addition to MTDH, identified as an important contributor to aggressiveness, the other genes might represent markers for tumor growth potential and possible targets for drug therapy.

The concept of peptide-based vaccines against cancer has made noteworthy progress. Metadherin (MTDH) overexpression and its role in the development of diverse cancers make it an attractive target for cancer immunotherapy. In the current study, six different T cell epitope prediction tools were run to identify MTDH peptides with multiple immunogenic regions. Further, molecular docking was performed to assess HLA-peptide binding interactions. Nine and eleven peptides fragments containing multiple CD8 (+) and CD4 (+) T-cell epitopes, ranging from 9 to 20 amino acids, respectively, were obtained using a consensus immunoinformatics approach. The three peptides that were finally identified as having overlapping CD4 (+) and CD8 (+) T- cell epitopes are ARLREMLSVGLGFLRTELG, FLLGYGWAAACAGAR, YIDDEWSGLNGLSSADP. These peptides were found to not only have multiple T cell epitopes but also to have binding affinity with wide HLA molecules. A molecular docking study revealed that the predicted immunogenic peptides (with single or multiple T cell epitopes) of MTDH have comparable binding energies with naturally bound peptides for both HLA classes I and II. Thus, these peptides have the potential to induce immune responses that could be considered for developing synthetic peptide vaccines against multiple cancers.

Osteosarcoma (OS) is a primary malignant tumor of bone tissue. Effective chemotherapy may improve the survival of patients with OS. MicroRNAs (miRs) serve significant roles in the regulatory function of tumorigenesis and chemosensitivity of different types of cancer. miR‑22 has been revealed to inhibit the proliferation and migration of OS cells, as well as increasing their sensitivity to cisplatin (CDDP). The mechanisms of action behind the functions of miR‑22 in OS drug resistance require investigation. Therefore, in the present study, the human OS cell lines (MG‑63, U2OS, Saos2 and OS9901) and a drug‑resistant cell line (MG‑63/CDDP) were cultured. Cell proliferation, apoptosis and autophagy assays were performed to investigate the proliferation, apoptosis and autophagy of cell lines transfected with miR‑22 mimic. Reverse transcription‑quantitative polymerase chain reaction and western blot analysis were performed to investigate the expression levels of associated genes. The results revealed that miR‑22 inhibited the proliferation of MG‑63 cells and MG‑63/CDDP cells, and enhanced the anti‑proliferative ability of CDDP. miR‑22 induced apoptosis and inhibited autophagy of MG‑63 cells and MG‑63/CDDP cells. Apoptosis‑related genes, including caspase‑3 and Bcl‑2‑associated X protein were upregulated, while B‑cell lymphoma‑2 was downregulated in both cell lines transfected with the miR‑22 mimic. Autophagy protein 5, beclin1 and microtubules‑associated protein 1 light chain 3 were downregulated in both cell lines transfected with miR‑22 mimic. Furthermore, the in vitro and in vivo expression levels of metadherin (MTDH) in the OS/OS‑CDDP‑resistant models were downregulated following transfection with the miR‑22 mimic. Therefore, the results of the present study suggested that miR‑22 promoted CDDP sensitivity by inhibiting autophagy and inducing apoptosis in OS cells, while MTDH may serve a positive role in inducing CDDP resistance of OS cells.

Non-small-cell lung cancer (NSCLC) is an aggressive neoplasm with a poor survival and novel therapies are urgently needed. The study of deregulated micro- RNAs (dereg-miRs) could constitute a strategy helping to detect specific genes playing a relevant role in the disease. Thus, the oncoproteins encoded by these genes could be exploited as novel therapeutic targets to be inhibited by small molecules, aptamers, or monoclonal antibodies.

The present review is focused on candidate genes having convincing biological evidences to be both bona fide targets for dereg-miRs and playing a role in NSCLC progression. These genes were evaluated according to the molecular pathway they belong. Moreover, in the attempt to provide an even broader list of candidate therapeutic targets for NSCLC, the full list of genes was analyzed using the online tool Interactome DB.

Among the identified targets, some of them belong to p53 or MAP kinase signaling pathways, and others include caspases, MCL1, and BCL2L2 (playing a role in apoptosis), ZEB1, ZEB2, and USP25 (epithelial-to-mesenchymal transition), EZH2, SOX9, and HOXA5 (differentiation), Paxillin, LIMK1 and MTDH (cytoskeleton remodeling), and HDGF (angiogenesis). In addition, other targets, such as TIMP-2, PIM-1, and components of the IGF-signaling pathways were suggested following the interactome analysis.

Studies on dereg-miRs helped to identify a set of genes whose encoded proteins could constitute candidates for future therapeutic approaches.

Mannitol dehydrogenase (MtDH) is a key enzyme controlling the reductive synthesis of mannitol from fructose in the common mushroom Agaricus bisporus. A better understanding of the control of mannitol metabolism can be obtained by studying the structure of this enzyme. Here, the purification and crystallization of recombinant MtDH are reported. Crystals generally belonged to the space group C2, with unit-cell parameters a = 227, b = 125, c = 133 A, beta = 118 degrees, and diffracted to at least 1.8 A resolution, although a tantalum derivative belonged to the space group P2(1) and diffracted to the lower resolution of 2.9 A.

BACKGROUND

Cluster headache is a severe headache disorder with unknown aetiology. The pathophysiology and symptoms present certain common features with migraine. Specifically, activation of the trigeminal vascular system seems to be involved in both disorders, which is hypothesized to result in neurogenic inflammation and vasodilation of the cerebral vessels. In addition, genetic factors have been implicated in both migraine and cluster headache.

OBJECTIVE

In order to determine whether or not migraine and cluster headache share genetic risk factors, we screened two genetic variants known to increase the risk of migraine in Sweden in a Swedish cluster headache case-control study population.

METHODS

In all, 541 patients and 581 control subjects were genotyped for rs1835740 in close proximity to MTDH (metadherin) and rs2651899 in the PRDM16 (PR/SET domain 16) gene, using TaqMan® real-time PCR and pyrosequencing. In addition, we analyzed MTDH gene expression in a subset of the material, using reverse transcription real-time PCR to determine relative mRNA levels in primary fibroblast cell lines from patients and controls.

RESULTS

We found a trend for association between rs1835740, which is reported to affect MTDH mRNA levels, and cluster headache in our Swedish case-control material (p = 0.043, Χ2 = 4.102). This association was stronger in a subgroup of patients suffering from both cluster headache and migraine (p = 0.031, Χ2 = 6.964). We could further confirm that rs1835740 has an effect on the transcriptional activity of MTDH. In this Swedish cluster headache cohort we did not find an association with the rs2651899 variant.

CONCLUSIONS

We conclude that rs1835740 is a potential risk factor for cluster headache in Sweden. Our data indicates that rs1835740 and MTDH might be involved in neurovascular headaches in general whilst rs2651899 is specifically related to migraine.

We and others recently identified the gene metadherin (MTDH) as a functional driver in multiple aspects of cancer progression. It is overexpressed in cancer cells originating from a variety of tissues, partially due to DNA amplification of the chromosomal 8q22 region where this gene resides. The rapidly accumulated data from MTDH studies of the past several years have documented its role in tumorigenesis, angiogenesis, cell proliferation, survival, anchorage-independent growth, metastasis and chemoresistance. In particular, it simultaneously helps the primary tumor cells to survive conventional chemotherapy and spread to distant organs, both of which are major contributors to cancer therapy failure and ultimately patient death. The efforts to elucidate the molecular mechanism of MTDH functions led to observations indicating its involvement in several prominent cancer-related signaling pathways including Ras, c-Myc, PI3K/AKT, NF-κB, Wnt/β-catenin, and more recently, microRNA machinery. Herein we will briefly summarize the studies that establish MTDH as a promising target for cancer therapeutics.

Osteosarcoma is the most common primary malignant tumor, especially in children and adolescents. Circular RNAs (circRNAs) are found to play roles in the progression of osteosarcoma. However, the exact functions of circRNAs in osteosarcoma development still need to be clarified. We obtained differentially expressed circRNAs and miRNAs from a GSE99671 data set (GEO database). The gene co-expression network of ceRNAs and osteosarcoma-related genes was analyzed using the STRING database. qRT-PCR was used to detect the expression of circ-03955 and miR-3662. Transwell assays and flow cytometry were performed to detect phenotypic changes in cell function. A xenograft tumor model was established using BALB/c nude mice. Dual luciferase activity and RNA immunoprecipitation assays were performed to assess the relationship between circ-03955, miR-3662, and metadherin (MTDH). Immunohistochemistry, immunofluorescence, and Western blotting were used to assess protein expression levels. Circ-03955 was significantly upregulated, and miR-3662 was downregulated in osteosarcoma. Circ-03955 silencing inhibited the growth and metastasis of osteosarcoma. Mechanism analysis revealed that circ-03955 could bind to miR-3662, and the latter could target MTDH, leading to its suppressed expression and facilitating epithelial-mesenchymal transition (EMT). All these findings demonstrate that the presence of circ-03955 promotes EMT in osteosarcoma by acting as miR-3662 sponge-mediated MTDH expression.

Keywords: circ-03955; epithelial-mesenchymal transition; metadherin; miR-3662; osteosarcoma.

We report a case of a 38-year-old mold-allergic patient who developed episodes of generalized urticaria and systemic anaphylactic shock immediately after ingesting button mushrooms. A manganese-dependent superoxide dismutase (MnSOD) and a NADP-dependent mannitol dehydrogenase (MtDH) from Agaricus bisporus mushroom were identified as patient-specific IgE-binding proteins. Cross-reactivity between A. bisporus MnSOD and mold aeroallergens was confirmed. We conclude that prior sensitization to mold aeroallergens might explain severe food reactions to cross-reacting homologs mushroom proteins.

The B-cell receptor (BCR) signaling pathway serves an important role in the pathogenesis of chronic lymphocytic leukemia (CLL), and has been identified as a novel and effective therapeutic target of CLL, with particular focus its kinase factor, BTK. Previous studies have focused on combining the BTK inhibitor with additional chemotherapeutic agents to improve the prognosis of patients with CLL. Further investigation into the mechanism of the BTK inhibitor would promote an understanding of the pathogenesis of CLL. The current study investigated the association between ibrutinib and the Wnt signaling pathway, additionally focussing upon one of its regulators, metadherin (MTDH), which has been identified to be overexpressed in CLL and is considered a promoter of the Wnt pathway. The experiments in the current study were performed in the MEC-1 CLL cell line. Results indicated that MTDH, β-catenin and lymphoid-enhancing factor-1 were inhibited subsequent to ibrutinib treatment. The results indicate that in CLL, ibrutinib is likely to possess an inhibitory role in Wnt signaling.

BACKGROUND Reports show that ultrasound-targeted microbubble destruction (UTMD) is a promising method of gene therapy, and metadherin (MTDH) is related to the development of breast cancer. Thus, we investigated the role of MTDH in breast cancer and compared the effect of suppressing MTDH by shRNA using liposome, UTMD, or the combination of these 2 methods. MATERIAL AND METHODS Graphing of survival curves of MTDH was analyzed by bioinformatics. UTMD was conducted using an ultrasonic therapeutic apparatus. Cell counting kit-8 (CCK-8) assay was used to measure cell viability. Migration and invasion rates were measured by wound healing test and Transwell invasion assay, respectively. The expression of MTDH, E-cadherin, metastasis-associated protein-1 (MTA-1), matrix metalloproteinase (MMP)-2, and MMP-9 were measured by Western blot and qPCR. RESULTS The prognosis of breast cancer can be decreased by the high expression of MTDH, and elevated expression of MTDH was discovered in MCF-7, MCF-10A, and T47D cell lines. UTMD combined with liposome is most efficient in transfecting shRNA, clearly suppressing the expression of MTDH and thereby decreasing cell viability, migration, invasion rate, and epithelial- mesenchymal transition (EMT) processes in the MCF-7 cell line. CONCLUSIONS UTMD combined with liposome could be used as a more efficient way to transfect shRNA into cells to suppress the expression of MTDH and thus lead to the downregulation of proliferation, migration, and EMT processes of the MCF-7 cell line, showing the potential for use in gene therapy.

Ovarian cancer (OC) is the most aggressive gynecological cancer. Even with the advances in detection and therapeutics, it still remains clinically challenging and there is a pressing need to identify novel therapeutic strategies. In searching for rational molecular targets, we identified metadherin (MTDH), a multifunctional gene associated with several tumor types but previously unrecognized in OC. In this study, we found the MTDH is overexpressed in OC tissues. Through in vitro assays with overexpression cells, we characterized the role of MTDH. We confirmed MTDH stable overexpression significantly increased the expression of TNF-α, IL-6, IL-8, IL-10, and IL-1β. Interestingly, NF-kappa-B (NF-κB) and MTDH were found in a feed-forward loop motif. Thus, our findings support the notion that the MTDH and NF-κB signaling network contributes to OC traits. MTDH represents a new OC-associated gene that can contribute to insights of OC biology and suggests other treatment strategies.

OBJECTIVE

To observe the expression changes of metadherin (MTDH) and matrix metalloproteinase-9 (MMP-9) in the laryngeal squamous cell carcinoma tissues and to investigate the significance.

METHODS

The expression of MTDH and MMP-9 in 54 cases of laryngeal squamous cell carcinoma tissues(observation group) and 30 cases of para-carcinoma tissues (control group) was examined by immunohistochemical method, the correlation between them and their correlations with the clinicopathological parameters were analyzed.

RESULTS

The positive expression rates of MTDH in the observation group and control group were 64.8% (35/54) and 6.7% (2/30), respectively; the positive expression rates of MMP-9 in the observation group and control group were 70.4% (38/ 54) and 13.3% (4/30), respectively; and there was a statistically significant difference between two groups (all P < 0.01). In the laryngeal squamous cell carcinoma tissues, the expression of MTDH protein was related with degree of differentiation, lymph-node metastasis and TNM stage (all P < 0.05); and the expression of MMP-9 protein was related lymph-node metastasis and TNM stage (all P < 0.05). The expression of MTDH was positively correlated with MMP-9 in the laryngeal squamous cell carcinoma tissues (r = 0.371, P < 0.01).

CONCLUSIONS

The high expression of MTDH and MMP-9 was closely related to the occurrence, development and metastasis of laryngeal squamous cell carcinoma, joint detection of the two proteins was valuable for early diagnosis and prognosis of laryngeal squamous cell carcinoma.

Background: Head and neck cancer (HNSCC) is one of the most lethal cancers characterized by high relapse and poor prognosis. Several miRNAs have been implicated in HNSCC, including the tumor suppressor miR-137. A large CpG island (CpG73) spans most of the miR-137 gene sequence and stretches 659-bp downstream, ending just upstream of miR-2682 in the same host gene. Here, we assessed the role of the MIR137/MIR2682 locus in HNSCC.

Methods: MiRNA expression was analyzed in paired cancerous and normal tissues from 77 HNSCC patients by Quantitative Reverse-Transcription PCR. CpG73 methylation in paired tissues from 48 patients was determined by Combined Bisulfite Restriction Analysis. Associations between expression and methylation levels and patient clinicopathological parameters were investigated.

Results: Decreased expression of miR-137 (p<0.01) and miR-2682 (p<0.01) precursors was observed in cancerous tissues, most significantly in oropharyngeal tumors. Lower miR-137 levels correlated with increased perineural invasiveness (p=0.04). Predicted common miRNA targets MTDH and Notch1 were upregulated in tumor tissues. The CpG73 region between miR-137 and miR-2682 was hypermethylated in tumors. Methylation was observed in 60.4% of cancerous compared to 31.6% of normal tissues, and methylation levels were significantly higher (p<0.01) in tumors. Increased methylation correlated with decreased disease-free patient survival (P=0.024).

Conclusion: The MIR137/MIR2682 locus correlated with HNSCC perineural invasiveness. This is the first report showing miR-2682 downregulation in head and neck cancer. Our results support the tumor suppressive role of miR-137 and miR-2682. The inverse correlation between CpG73 hypermethylation and disease-free survival suggests this epigenetic mark may have prognostic value in HNSCC.

Keywords: HNSCC; head and neck cancer; miR-137; miR-2682, CpG methylation.

The human microRNA 375 (MIR375) is significantly downregulated in human colorectal cancer (CRC) and we have previously shown that MIR375 is a CRC-associated miRNA. The metadherin (MTDH) is a candidate target gene of MIR375.

To investigate the interaction and function between MIR375 and MTDH in human CRC.

A luciferase reporter system was used to confirm the effect of MIR375 on MTDH expression. The expression levels of MIR375 and the target genes were evaluated by quantitative RT-PCR (qRT-PCR), western blotting, or immunohistochemistry.

MTDH expression was found to be upregulated in human CRC tissues compared to that in healthy controls. We show that MIR375 regulates the expression of many genes involved in the MTDH-mediated signal transduction pathways [BRAF-MAPK and phosphatidylinositol-4,5-biphosphate-3-kinase catalytic subunit alpha (PIK3CA)-AKT] in CRC cells. Upregulated MTDH expression levels were found to inhibit NF-κB inhibitor alpha, which further upregulated NFKB1 and RELA expression in CRC cells.

Our findings suggest that suppressing MIR375 expression in CRC regulates cell proliferation and angiogenesis by increasing MTDH expression. Thus, MIR375 may be of therapeutic value in treating human CRC.

In the present study, we isolated and purified one polysaccharide (TRP) from Trametes robiniophila, which had a backbone of 1,3,6- and 1,4-linked glucpyranosyl moieties, with 1-linked arabinofuranosyl and galactopyranosyl terminal at the O-3 position of 1,3,6-linked glucpyranosyl residues. TRP was further evaluated for its antitumor activity against xenografted U-2 OS osteosarcoma in BALB/c nude mice together with the possible mechanism of action. We found that oral administration of TRP significantly suppressed U-2 OS tumor growth in mice via the induction of apoptosis, as evidenced by the increased number of TUNEL-positive cells in tumor tissues. Moreover, TRP administration increased the levels of the proapoptotic Bax protein and decreased the level of the antiapoptotic Bcl-2 protein, thus resulting in a rise of Bax/Bcl-2 ratio. Furthermore, the protein expression of caspase-9, caspase-3 and cleaved PARP became evident in tumor tissues from mice following TRP treatment, but caspase-8 keep unchanged. Besides, overexpression of metadherin (MTDH) was attenuated in tumor tissues of TRP-fed mice. Taken together, these findings suggest that the TRP-induced apoptosis of tumor tissues is through a mitochondria-mediated intrinsic apoptotic pathway.

OBJECTIVE

To determine if Metadherin (MTDH) expression levels are positively correlated with the clinical stage of diffuse large B-cell lymphoma (DLBCL) based on MTDH being highly expressed in other type of tumors including melanoma, malignant glioma, breast cancer, and hepatocellular carcinoma. In this study, we investigated the pathologic significance of MTDH and its potential in predicting DLBCL outcomes.

METHODS

Tissue samples from 50 patients with DLBCL and 22 patients with lymph node reactive hyperplasia were collected and evaluated using immunohistochemical staining, microscopy, and western blotting. The Kaplan-Meier method and Cox regression model were used for survival analysis of patients.

RESULTS

Our results show that the overexpression of the MTDH protein in tissues was observed in 66% of patients with DLBCL, whereas it was not overexpressed in the patients with reactive hyperplastic lymph nodes. While there was no correlation between MTDH overexpression with age, sex, presence of B symptoms, and lactate dehydrogenase (LDH) levels in patients with DLBCL, this parameter was positively correlated with clinical stages. Moreover, MTDH-negative patients had significantly better prognoses compared with the MTDH-positive patients.

CONCLUSIONS

Our preliminary study indicates that MTDH may play an important role in the development of DLBCL, and that MTDH overexpression is potentially associated with the clinical progression of DLBCL. In addition, high expression levels of MTDH in tissues was correlated with a poorer prognosis for patients with DLBCL. As such, MTDH may be a potential therapeutic target for specific therapy. However, research on a larger group of patients is needed to verify these preliminary results.

Numerous microRNAs (miRNAs) are dysregulated in tongue squamous cell carcinoma (TSCC), and their dysregulation has been demonstrated to have a strong correlation with TSCC progression via regulation of their targets. Therefore, miRNAs have potential use in the diagnosis and treatment of patients with TSCC. In the present study, miRNA‑758 (miR‑758) expression in TSCC tissues and cell lines was detected through reverse transcription‑quantitative polymerase chain reaction, and the effects of miR‑758 on TSCC cell proliferation and invasion were investigated by using Cell Counting kit‑8 and Transwell invasion assays. A luciferase reporter assay was performed to determine the target interaction between miR‑758 and metadherin (MTDH) in TSCC cells. The results revealed that miR‑758 was downregulated in TSCC tissues and cell lines. miR‑758 overexpression restricted the proliferation and invasion of TSCC cells. Additionally, MTDH was verified as a direct target gene of miR‑758 in TSCC cells. Furthermore, MTDH was observed to be upregulated in TSCC tissues, and the upregulation of MTDH was inversely correlated with miR‑758 expression. Moreover, restored MTDH expression significantly counteracted the suppressive effects of miR‑758 overexpression on TSCC cells. These results suggested that miR‑758 may prevent TSCC progression and development by directly targeting MTDH, thereby providing evidence that miR‑758 is a novel therapeutic target for the treatment of patients with TSCC.

Ovarian cancer (OC) has a high mortality rate among women worldwide. However, even with the advances in detection and therapeutics, the number of cases is increasing worldwide. Increasingly, microRNAs (miRNAs), including miR-497-5p, have been implicated in the progression of many cancers, but the role of miR-497-5p in OC remains unknown. The purpose of this study was to investigate the underlying molecular mechanism of miR-497-5p in OC. Herein, we find that miR-497-5p is down-regulated in OC tissues, and overexpression of miR-497-5p enhances apoptosis in OC cells. The increased apoptosis was correlated with enhanced expression of apoptosis-related proteins. MiR-497-5p directly bound the 3'-untranslated region of metadherin (MTDH), leading to the reduction of MTDH in mRNA and protein levels. Moreover, MTDH knockout promoted the apoptosis of OC cells. Taken together, we conclude that miR-497-5p contributes to cell apoptosis in OC by regulating MTDH.

The colorectal carcinogenesis is a complex process encompassing genetic alterations. The oncoprotein AEG-1, encoded by the MTDH gene, was shown previously to be involved in colorectal cancer (CRC). The aim of this study was to determine the frequency and the spectrum of MTDH variants in tumor tissue, and their relationship to clinicopathological variables in CRC patients. The study included tumors from 356 unselected CRC patients. Mutation analysis of the MTDH gene, including coding region and adjacent intronic sequences, was performed by direct DNA sequencing. The corresponding normal colorectal tissue was analyzed in the carriers of exonic variant to confirm germline or somatic origin. We detected 42 intronic variants, where 25 were novel. Furthermore, we found 8 exonic variants of which four, one missense (c.977C>> G-germline) and three frameshift mutations (c.533delA-somatic, c.1340dupA-unknown origin, c.1731delA-unknown origin), were novel. In silico prediction analyses suggested four deleterious variants (c.232G>> T, c.533delA, c.1340dupA, and c.1731delA). There were no correlations between the MTDH variants and tumor stage, differentiation or patient survival. We described several novel exonic and intronic variants of the MTDH gene. The detection of likely pathogenic truncating mutations and alterations in functional protein domains indicate their clinical significance, although none of the variants had prognostic potential.

UNASSIGNED

Lobaplatin shows antitumor activity against a wide range of tumors, including metastatic breast cancer (BCa). The overexpression of metadherin (MTDH) is associated with poor prognosis of BCa patients. This study was designed to investigate the effect of lobaplatin on MCF-7 cell proliferation and its association with MTDH expression.

UNASSIGNED

Clinical treatment for BCa using lobaplatin, in combination with other general chemotherapy drugs, was administered to 32 BCa patients. The safety, effectiveness, and prognosis in lobaplatin-treated BCa patients were compared with those in controls (n=32). In vitro experiments were performed in MCF-7 cells to investigate the effect of lobaplatin on cell proliferation, apoptosis, and MTDH expression.

UNASSIGNED

We found the intraoperative local chemotherapy using lobaplatin was safe and effective for BCa treatment, in comparison with the patients administered general chemotherapy drugs. Treatment of MCF-7 cell cultures with lobaplatin significantly reduced cell proliferation and increased cell apoptotic percentage. The expression of MTDH and Bcl-2 was inhibited by lobaplatin and that of Bax was increased by lobaplatin. Moreover, we observed the inhibition of MTDH by shRNA reduced cell proliferation and enhanced cell apoptosis.

UNASSIGNED

Lobaplatin was a safe and effective adjuvant chemotherapy for BCa. The effect of lobaplatin on inhibiting MCF-7 cell proliferation and inducing cell apoptosis might be, as least in part, mediated by suppressing the expression of oncogene MTDH.