LY294002通过抑制胶质瘤的PI3K/Akt通路增强三氧化二砷毒性作用

LY294002 enhances cytotoxicity of ATO in glioma by down-regulation of the PI3K/Akt pathway

目的探讨LY294002通过抑制胶质瘤的PI3K/Akt通路增加三氧化二砷(arsenic trioxide,ATO)毒性作用。方法分别用不同剂量的LY294002检测胶质瘤细胞的相对增殖率、侵袭能力、凋亡能力和PI3K、p-AKT的蛋白表达情况。选择适合的与ATO作用的LY294002浓度。结果与单独药物处理组相比,LY294002联合ATO治疗组肿瘤细胞增殖明显受到抑制。药物联合组诱导细胞凋亡,以及降低了U251细胞的侵袭性。与单独ATO治疗组相比,药物联合治疗组中,凋亡相关蛋白cleaved-caspase3及Bax显著增加。LY294002使p-Akt及Bcl-2表达显著降低。结论 LY294002通过负调节PI3K/Akt通道提高了ATO对胶质瘤细胞的毒性作用。

Objective To explore the effect that LY294002 enhances cytotoxicity of arsenic troxide （ATO） in glioma by down-regulating the PI3K/Akt pathway. Methods U251 were treated with different concentrations of LY294002 and detected by MTF assay, cell invasion as- say, apoptosis assays, and protein expression of PI3K and p-AKT were detected. Cells were treated with ATO and combination a suitable concentrations of LY294002. Results Prolifera- tion of tumor cell was obviously suppressed by arsenic trioxide with LY294002 treatment than by either drug used alone. The combination treatment induced more apoptosis rate, while re- duced the invasive capability of U251 cells. The apoptosis-associated proteins cleaved-caspase3 and Bax were more significantly up-regulated by the combined treatment than arsenic trioxi- deused alone. While, p-Akt and Bel-2 which promoted the invasive capability of arsenic triox- ide, were significantly decreased by LY294002. Conclusion LY294002 enhances the cyto- toxicity of arsenic trioxide by down-regulation of PI3K/Akt pathway.