Qin Guangyi, Li Ping, Xue Zhuowei
Department of Obstetrics and Gynaecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Oncol Lett. 2018 Sep;16(3):3929-3934. doi: 10.3892/ol.2018.9074. Epub 2018 Jul 4.
Triptolide exhibits immunosuppressive, anti-inflammatory, antifertility and antineoplastic functions. However, the anticancer effect of triptolide on cervical cancer and the underlying mechanism remains to be fully understood. The present study assessed the mechanisms underlying the effect of triptolide on the viability and apoptosis of human cervical cancer cells. SiHa cells were treated with 12.5-100.0 nM triptolide for 12, 24 or 48 h. The present study demonstrated that triptolide inhibited viability and induced apoptosis in SiHa cells time- and dose-dependently. Furthermore, treatment with triptolide promoted autophagy and activated microtubule associated protein 1 light chain 3 α expression in SiHa cells. Triptolide treatment suppressed the expression of phosphorylated (p)-protein kinase B (Akt), p-mechanistic target of rapamycin (mTOR), and p-p70S6K, activated the expression of p-p38, mitogen-activated protein kinase (MAPK) and p53 and inhibited the expression of p-forkhead box O3 (Foxo3a) in SiHa cells. These results suggested that triptolide induces protective autophagy, suppresses cell viability and promotes apoptosis in human cervical cancer cells by inducing the autophagy-targeting phosphoinositide 3-kinase/Akt/mTOR, p38, MAPK, p53 and Foxo3a pathways.
雷公藤甲素具有免疫抑制、抗炎、抗生育和抗肿瘤功能。然而，雷公藤甲素对宫颈癌的抗癌作用及其潜在机制仍有待充分了解。本研究评估了雷公藤甲素对人宫颈癌细胞活力和凋亡影响的潜在机制。将SiHa细胞用12.5 - 100.0 nM雷公藤甲素处理12、24或48小时。本研究表明，雷公藤甲素在SiHa细胞中对活力的抑制和凋亡的诱导呈时间和剂量依赖性。此外，雷公藤甲素处理促进了自噬并激活了SiHa细胞中微管相关蛋白1轻链3α的表达。雷公藤甲素处理抑制了磷酸化（p）-蛋白激酶B（Akt）、p-雷帕霉素靶蛋白（mTOR）和p-p70S6K的表达，激活了p-p38、丝裂原活化蛋白激酶（MAPK）和p53的表达，并抑制了SiHa细胞中p-叉头框O3（Foxo3a）的表达。这些结果表明，雷公藤甲素通过诱导靶向自噬的磷酸肌醇3-激酶/ Akt / mTOR、p38、MAPK、p53和Foxo3a途径，诱导保护性自噬，抑制细胞活力并促进人宫颈癌细胞凋亡。
