Xie Xina, Lin Jiatian, Zhong Yuantang, Fu Mianheng, Tang Aifa
Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, Guangdong 510080, P.R. China.
Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen, Guangdong 518035, P.R. China.
Exp Ther Med. 2019 Aug;18(2):1226-1234. doi: 10.3892/etm.2019.7672. Epub 2019 Jun 13.
Fibroblast growth factor receptor 3 (FGFR3) is a high frequency mutant gene in bladder cancer (BCa) and has become a promising therapeutic target due to its involvement in cell proliferation and migration. However, whether and how FGFR3 mutations affects BCa cell chemosensitivity is unknown. The current study aimed to elucidate the role of the FGFR3 mutation in the development of chemoresistance in BCa cells. The results revealed that 97-7 (FGFR3) cells had decreased sensitivity to cisplatin compared with 5637 (FGFR3) and T24 (FGFR3) cells. The ratio of phosphorylated-Akt/total-Akt was higher in 97-7 (FGFR3) cells, which was reversed by knockdown of FGFR3. Furthermore, inhibition of Akt signaling by GDC0068 or LY294002 increased the cisplatin sensitivity of 97-7 (FGFR3) cells. GDC0068 or LY294002 was also revealed to augment the effects of cisplatin on 97-7 (FGFR3) cell proliferation and apoptosis. The results of the present study demonstrated that the FGFR3 mutation promotes chemoresistance in BCa cells by activating the Akt signaling pathway. The FGFR3 mutation may therefore be used as a predictor of chemosensitivity in patients with BCa.
成纤维细胞生长因子受体3（FGFR3）是膀胱癌（BCa）中高频突变的基因，由于其参与细胞增殖和迁移，已成为一个有前景的治疗靶点。然而，FGFR3突变是否以及如何影响BCa细胞的化学敏感性尚不清楚。本研究旨在阐明FGFR3突变在BCa细胞化疗耐药发展中的作用。结果显示，与5637（FGFR3）和T24（FGFR3）细胞相比，97-7（FGFR3）细胞对顺铂的敏感性降低。97-7（FGFR3）细胞中磷酸化Akt/总Akt的比例较高，而FGFR3的敲低可使其逆转。此外，GDC0068或LY294002对Akt信号的抑制增加了97-7（FGFR3）细胞对顺铂的敏感性。还发现GDC0068或LY294002增强了顺铂对97-7（FGFR3）细胞增殖和凋亡的作用。本研究结果表明，FGFR3突变通过激活Akt信号通路促进BCa细胞的化疗耐药。因此，FGFR3突变可作为BCa患者化学敏感性的预测指标。
