Radix ranunculus temate saponins sensitizes ovarian cancer to Taxol via upregulation of miR-let-7b.

Abstract

A common cause of treatment failure in ovarian cancer is acquired drug resistance. Therefore, effective novel drugs against chemoresistance need to be developed. MicroRNAs (miRNAs or miRs) serve key regulatory roles in tumorigenesis and chemoresistance. The objective of the present study was to explore the role of miR-let-7b in ovarian cancer chemoresistance, and to develop novel strategy for the treatment of drug-resistant ovarian cancer. For this purpose, reverse transcription-quantitative PCR was performed to evaluate the expression level of miR-let-7b in fresh ovarian cancer tissues and cell lines. miR-let-7b mimic was transfected into ovarian cancer cell lines. Functional experiments, cell apoptosis and cell viability assays were carried out to identify the tumor-suppressor function of miR-let-7b. The treatment effect of Radix ranunculus temate saponins (RRTS), one of the primary constituents extracted from the traditional Chinese medicine radix Ranunculi ternati, was identified in vitro and in vivo. The results revealed that miR-let-7b was downregulated significantly in chemoresistant ovarian cancer patients. miR-let-7b overexpression suppressed cell growth and invasion and enhanced sensitivity to Taxol of ovarian cancer cells. Furthermore, miR-let-7b levels in ovarian cancer tissue were inversely associated with collagen type III α1 chain (COL3A1) levels. COL3A1, a non-fibrillar collagen associated with chemoresistance, was targeted by miR-let-7b. RRTS showed cytotoxic effects on ovarian cancer cells through inducing miR-let-7b expression and decreasing COL3A1 expression. In addition, RRTS sensitized ovarian cancer to Taxol both in vitro and in vivo. In conclusion, the present results revealed synergistic cytotoxicity of RRTS and Taxol on against ovarian cancer cells via upregulating expression of miR-let-7b. Combination of Taxol and RRTS may be a novel treatment strategy for patients with TR ovarian cancer.