目的雪胆素甲(CuⅡa)诱导肺癌NCI-H460和A549的凋亡效应及其作用机制初探。方法利用CCK-8检测CuⅡa对肿瘤细胞抑制活性;流式细胞术检测CuⅡa对肿瘤细胞凋亡以及周期的影响;Western blot检测CuⅡa对Aurora A、STAT3以及Cofilin蛋白磷酸化的影响。结果 CuⅡa对肺癌细胞NCI-H460和A549具有明显抑制作用,其IC50分别为224.9和108.3 nmol·L^-1;CuⅡa能诱导肿瘤细胞凋亡,并阻滞细胞周期于G2/M期;Western blot实验结果显示CuⅡa对STAT3和Cofilin的磷酸化具有抑制作用,且呈现剂量依赖性,CuⅡa能抑制Aurora A磷酸化,符合Aurora A激酶抑制剂抗肿瘤效应重要特征—阻滞细胞于G2/M期。结论CuⅡa对非小细胞肺癌细胞系NCI-H460和A549具有明显的抑制作用,CuⅡa可作为抗非小细胞肺癌的先导化合物进行下一步研究。
Aim To study the apoptosis effect of cucurbitacin Ⅱ a on non-small cell lung cancer cell lines NCI-H460 and A549 and its underlying mechanism.Methods Cell viability was assessed by CCK-8 assay.The apoptosis effect and cell cycle arrest were detected by Flow cytometry.Western blot was employed to detect the related protein.Results The proliferation of lung cancer cell lines NCI-H460 and A549 was inhibited by CuⅡa,which showed cytotoxic activity with IC50 values of 224.9 nmol·L^-1and 108.3 nmol·L^-1against NCI-H460 and A549 respectively.Cu Ⅱ a induced the cells apoptosis and cell cycle arrest at G2/M phase.The results of Western blot showed Cu Ⅱ a inhibited the phosphorylation of STAT3 and Cofilin in a dose-dependent manner.Further,CuⅡa inhibited the phosphorylation of Aurora A,in line with the important characteristics of anti-tumor effect of Aurora A kinase inhibitor with blocking cells in the G2/M phase.Conclusion Cu Ⅱ a has obvious anti-tumor effect against non-small cell lung cancer,which suggests its value as a lead compound for lung cell carcinoma.