关键词: 二甲双胍；上皮间质转化；前列腺肿瘤；Vcap；miR30a

Abstract:

Objective   To investigate the effects of metformin on proliferation, invasion and epithelial-mesenchymal transition (EMT) of prostate cancer Vcap cells and the possible miRNA-based mechanisms. Methods    Vcap cells that were treated with PBS were used as control group. MTS assay was used to determine cellular proliferation of Vcap cells treated by metformin with various concentrations (1-50mmol/L). Flow cytometric analysis was performed to detect cell cycle distributions. Wound healing assay and martrigel invasion assay were performed to evaluate invasive capacity of cancer cells treated by 5mmol/L metformin and miR30a; RT-PCR and Western blotting were used to detect mRNA and protein expression levels of epithelium markers (β-catenin, E-cadherin) as well as mesenchymal marker (Vimentin, N-cadherin). RT-PCR was used to detect the expression levels of miR30a, miR143, miR185, miR196b and miR205. Results   Metformin significantly inhibited proliferation of Vcap cells in a dose- and time-dependent manner. 5mmol/L metformin significantly influenced cell cycle distribution and inhibited invasiveness and motility capacity of Vcap cells. Metformin upregulated expression of E-cadherin (P<0.05) and β-catenin (P<0.05), but downregulated Vimentin (P<0.05) and N-cadherin (P<0.05) expression at mRNA and protein levels in Vcap cells. Significant upregulation of miR30a expression levels by metformin was identified (P<0.05) and further experiments confirmed that miR30a significantly inhibited proliferation and EMT of Vcap cells. Conclusion    Metformin significantly inhibits cell proliferation, invasion and EMT in prostate cancer Vcap cells. This process may involve upregulation of miR30a by metformin.

Key words: Metformin; Epithelial-mesenchymal transition; Prostatic neoplasia; Vcap; miR30a