RNA interference targeting CHFR enhances taxol chemosensitivity in endometrial cancer cells

Abstract

In recent years, it has been reported that CHFR may be a useful biomarker for chemotherapeutic response to microtubule inhibitors in some tumor cells. The purpose of the present study was to test the hypothesis and to elucidate the underlying mechanism in endometrial cancer cells. First, we effectively inhibited CHFR expression at both the mRNA and protein levels using siRNA targeting the CHFR gene in Ishikawa and Hec-1a cells. We found that inhibition of CHFR expression significantly enhanced the cytotoxicity of taxol to both cell types, which was confirmed again by colony formation assays. Moreover, suppression of CHFR induced a significant increase of the mitotic index and much lower numbers of cells at the G 2/M phase in both cells treated with taxol, indicating mitotic checkpoint impairment. On the other hand, the number of apoptotic cells significantly increased in Ishikawa and Hec-1a cells transfected with CHFR siRNA after treatment with taxol, which was associated with cyclin B1 nuclear localization. Our data indicate that RNA interference targeting CHFR can sensitize endometrial cancer cells to taxol and CHFR may be a promising molecular target to enhance the therapeutic effect of taxol for endometrial cancer.