FL118, a novel anticancer compound, inhibits proliferation and migration of ovarian cancer cells via up-regulation of cytoglobin in vivo and in vitro

Abstract

Background: FL118, a novel camptothecin analogue, exhibits strong anticancer activity on colon, head-and-neck and non-small cell lung cancer. However, its anti-tumor effects on ovarian cancer and the mechanism behind these effects still remain unclear. In this study, we aimed to assess the growth of ovarian cancer cells after FL118 administration in vivo and in vitro and whether cytoglobin (CYGB) plays a role in this analogue’s cancer-fighting potency. Methods: MTT and Wound-healing assay were used to detect cell proliferation and migration in ES-2 and SK-O-V3 cell lines after FL118 treatment, following CYGB-siRNA transfection. A tumor xenograft in nude mice was utilized to test the antitumor activity of FL118 in ovarian cancer. qRT-PCR and Western Blot were performed to detect mRNA and protein expression, respectively. Results: FL118 effectively inhibited the cell proliferation and migration of ES-2 and SK-O-V3 cells in a dose-dependent manner. CYGB siRNA knockdown led to a partial recovery of the proliferation and migration of both ES-2 and SK-O-V3 cells. Furthermore, FL118 exhibits a superior antitumor effect compared to topotecan in the nude mice bearing the ovarian cancer cell line of ES-2, along with the upregulation of CYGB expression. Conclusions: FL118 effectively inhibits the proliferation and migration of ovarian cancer cells by upregulating CYGB expression in vitro and in vivo , which provides new insight on FL118’s anti-tumor mechanism and its further clinical application.