Abstract
The PI3K/AKT/mTOR signaling pathway is considered as a promising therapeutic target in the treatment of ovarian cancer (OC); however, inhibition of this pathway only exhibited moderate clinical efficacy when tested clinically. Combination of mTOR inhibitors with other anticancer compounds could improve the anticancer efficiency. Therefore, the concurrent inhibition of Fibroblast Growth Factor Receptor (FGFR) signaling pathway was evaluated in the present study. OC cell lines were treated with FGFR inhibitor BGJ398, mTOR inhibitor Rapamycin, or combined inhibition of both BGJ398 and Rapamycin. The results revealed that the growth and motility, expression of angiogenic markers and phosphorylation of associated proteins were affected in treated OC cells. Additionally, the anticancer effects of aforementioned inhibitors were evaluated using a murine tumor xenograft model. Combined treatment with BGJ398 and Rapamycin exhibited stronger inhibitory effects on the growth and motility of OC cells compared with BGJ398 or Rapamycin alone group. Furthermore, combined inhibition of FGFR and mTOR pathways by BGJ398 and Rapamycin induced remarkable cell cycle arrest and apoptosis in OC cells. Reduced tumor size in the xenograft was also observed following combined treatment but not in BGJ398 or Rapamycin alone group. The results in the present study revealed that combined inhibition of FGFR and mTOR pathways could be a promising therapeutic strategy in the treatment of patients with OC.