Bufalin inhibits ovarian carcinoma via targeting mTOR/HIF-α pathway

Ovarian cancer is a severe health threat for women with increased incidence and stymied development in diagnosis and therapy. Drug resistance is still a big challenge. Bufalin is a multi-functional steroid-like compound extracted from natural product Chansu and has been tested as antitumour agent recently. The application and mechanism of bufalin in ovarian cancer remain unclear yet. Bufalin was first examined in ovarian epithelial cancer cell as well as primary ovarian tissue to evaluate its inhibitory activity in cell growth and migration, followed by the validation in xenograft tumour model and the patient samples. Bufalin is well tolerated by normal ovarian tissue at up to 40 μM and suppresses the cell growth and migration at 10 μM and xenograft tumour growth at 0.1mg/kg dosage. Bufalin inhibits the mammalian target of rapamycin (mTOR) activation and subsequently decreases hypoxia-induced factor 1 alpha (HIF-1α) level. Overexpression of HIF-1α could abolish the pro-apoptotic and antimigration activity of bufalin in cell culture. Strikingly, low HIF-1α level was correlated with improved responsiveness to cisplatin treatment in ovarian cancer patients. Bufalin was a potent inhibitor of cell growth and migration in ovarian cancer cells through suppression of mTOR activation and HIF-1α induction. Bufalin could be used to enhance the efficacy of cisplatin in ovarian cancer patients.