The purpose of the current study was to investigate whether metformin can enhance the anti-cancer effect of cisplatin on epithelial ovarian cancer in vitro and in vivo. CCK-8 assays were performed to detect cell viability, and flow cytometry was performed to measure cell apoptosis rates. Transwell assays were used to detect the migration and invasion ability of ovarian cancer cells. Western blotting and qRT-PCR were performed to detect protein expression. Xenograft mouse models were constructed to clarify the treatment response in vivo. Metformin alone or cisplatin alone dose-dependently inhibited SKOV3 and Hey cell proliferation. The combination of these two drugs exerted a stronger inhibitory effect with a higher apoptosis rate than administration of either drug alone. Transwell assay results revealed that metformin promoted the inhibitory effect of cisplatin on ovarian cancer cell metastasis. Metformin and cisplatin co-treatment significantly inhibited N-cadherin and MMP-9 expression. The Western blotting results revealed that metformin and cisplatin co-treatment inhibited TGFβ1 expression and Smad2 and Smad3 phosphorylation. The in vivo study results were consistent with results from the in vitro study. Data from our study suggest that metformin enhanced the anti-tumour effect of cisplatin on epithelial ovarian cancer in vitro and in vivo, which provides more evidence supporting the use of metformin to treat epithelial ovarian cancer.
Keywords: TGFβ; cisplatin; epithelial ovarian cancer; metastasis; metformin.