目的 探讨姜黄素联合雷帕霉素对去势难治性前列腺癌(CRPC)Pten-CaP8细胞增殖、自噬及凋亡的影响。方法 将不同浓度的姜黄素单独或与雷帕霉素共同处理Pten-CaP8细胞24 h后,MTT法检测细胞增殖,光镜下观察细胞形态,Westernblotting法检测相关蛋白表达。结果 姜黄素联合雷帕霉素可显著抑制Pten-CaP8细胞增殖(P<0.05),上调LC3-II/LC3-I表达,诱导PARP裂解,还可下调p-AKT(S473)、p-S6(S240/244)、AR(N-20)和Cyclin D1蛋白表达水平,使Pten-CaP8细胞形态变短且胞浆内出现空泡改变。结论 姜黄素联合雷帕霉素可共同诱导Pten-CaP8细胞自噬及凋亡且效果显著,两者协同抗癌机制与其拮抗PI3K/Akt/mTOR信号通路相关。

Objective To investigate the effects of curcumin combined with Rapamycin on cell proliferation, autophagy, and apoptosisin Pten-CaP8 cells of castration refractory prostate cancer (CRPC).Methods Cells were treated by different concentrations ofcurcumin with or without Rapamycin for 24 h. Cell proliferation was analyzed by MTT. Cell morphology was detected by lightmicroscopy. Expression of cell protein was evaluated by Western blotting. Results Curcumin combined with Rapamycin couldsignificantly inhibit the Pten-CaP8 cell proliferation (P < 0.05), up-regulate LC3-II/LC3-I, induce PARP cleavage, and down-regulatethe protein expression levels of p-AKT (S473), p-S6 (S240/244), AR (N-20), and Cyclin D1. Treated cells became short and changed tocytoplasmic vacuoles.Conclusion Through the induction of autophagy and apoptosis simultaneously, curcumin combined withRapamycin exerts synergistic antitumor activities correlated to the inhibition of PI3K/Akt/mTOR signaling pathways.

国家自然科学基金资助项目(30672757)