BEZ235对非小细胞肺癌A549细胞的放射增敏作用

Radiosensitization Effects of Inhibitor BEZ235 on NSCLC A549 Cells

目的采用双PI3K/mTOR抑制剂BEZ235联合放疗的方法,评价BEZ235对非小细胞肺癌A549细胞的放射增敏作用。方法分别采用单纯放疗和BEZ235联合放疗作用于A549细胞,MTT测定BEZ235对A549细胞的抑制作用,并计算半数抑制浓度(IC50);克隆形成实验评估BEZ235对A549细胞放射敏感性的影响;Western blotting检测AKT、pAKT蛋白的表达水平。结果BEZ235可以剂量依赖性抑制A549细胞的增殖,IC50为1.56μmol·L-1;实验组细胞存活分数(SF)显著低于对照组(P<0.05);实验组pAKT蛋白表达水平显著低于对照组(P<0.05)。结论BEZ235可通过抑制PI3K/AKT/mTOR信号通路的激活,从而抑制非小细胞肺癌A549细胞的增殖,并提高其放射敏感性。

Objective To evaluate the role of dual PI3K/mTOR inhibitor BEZ235 on the non-small cell lung cancer(NSCLC)A549 cells when combined with radiation therapy.Methods The A549 cells were treated with radiotherapy alone or in combination with BEZ235.The inhibition rate of BEZ235 on A549 cells was determined by MTT assay and the IC50 was calculated.The effect of BEZ235 on the radiosensitivity of A549 cells was assessed by colony formation assay,and the expression levels of AKT and pAKT proteins were analyzed by Western blotting.Results BEZ235 inhibited the proliferation of A549 cells in a dose-dependent manner with an IC50 of 1.56μmol·L-1.The surviving fraction(SF)of the combination group was significantly lower than that of the radiotherapy alone group.The expression level of pAKT protein in the combination group was significantly lower than in the radiotherapy alone group.Conclusion BEZ235 inhibited the proliferation and improved the radiosensitivity of A549 cells by suppressing the activation of PI3K/AKT/mTOR signaling pathway.