Kaempferol-3-O-rutinoside inhibits ovarian cancer by modulating FOXO3a to regulate integrin beta 1 and p-STAT3/Bcl-2

Abstract Although ovarian cancer has long been recognized as a serious threat to women's health worldwide, major questions remain about effective treatment. Plants are considered as a huge resource for searching anti-cancer compounds. In previous studies, the plant-derived agent kaempferol-3-O-rutinoside (KR) was shown to have anti-tumor effects on lung cancer, colon cancer, and malignant melanoma. However, its mechanism of action is not well understood. Here, we demonstrated that KR inhibited expression of integrin beta 1 and suppressed the motility and adhesion ability of ovarian cancer cells. Anoikis resistance of ovarian cancer cells was inhibited by KR through suppression of the p-STAT3/Bcl-2 axis. KR also increased the expression of FOXO3a. And inhibition of FOXO3a abrogated the effect of KR on integrin beta 1 and the p-STAT3/Bcl-2 axis in ovarian cancer. In addition, KR did not affect normal cells, even at high concentrations. These results revealed that activation of FOXO3a is a good target for ovarian cancer therapy, and that KR is a potential candidate compound for the treatment of ovarian cancer.