AZD9291通过抑制PI3K-AKT-mTOR通路抑制鼻咽癌细胞的增殖和迁移

AZD9291 suppresses proliferation and migration of nasopharyngeal carcinoma cells by inhibiting the PI3K-AKT-mTOR pathway

目的探讨AZD9291对鼻咽癌细胞增殖和迁移的影响。方法体外培养鼻咽癌HNE1和CNE2Z细胞,在HNE1细胞加入浓度分别为0、0.5、1、2、4、8μmol/L的AZD9291,CNE2Z细胞加入分别为0、1、2、4、8、16μmol/L的AZD9291。采用CCK8法检测细胞存活率;集落克隆实验检测AZD9291对细胞的增殖抑制作用;细胞划痕实验和Transwell实验检测细胞修复和迁移能力;Westernblot法检测EGFR相关信号通路蛋白及迁移相关蛋白的表达。结果CCK8和集落克隆实验结果显示AZD9291可显著抑制HNE1和CNE2Z细胞增殖(P<0.01);细胞划痕实验和Transwell实验结果显示AZD9291抑制HNE1和CNE2Z细胞迁移能力(P<0.01);Westernblot结果显示,随着浓度增加,AZD9291可通过调控EGFR下游PI3K-AKT-mTOR信号通路磷酸化蛋白的下调(P<0.01),抑制HNE1和CNE2Z细胞迁移(P<0.01)。结论AZD9291可通过抑制EGFR/PI3K/AKT/mTOR信号通路,抑制鼻咽癌HNE1和CNE2Z细胞的增殖并降低其修复和迁移能力,为后续AZD9291尝试用于鼻咽癌的治疗提供依据。

Objective To investigate the effects of AZD9291 on the proliferation and migration of nasopharyngeal carcinoma cells.Methods Nasopharyngeal carcinoma HNE1 and CNE2Z cells were treated with AZD9291 at the doses of 0.5,1,2,4,and 8μmol/L and at the doses of 1,2,4,8,and 16μmol/L,respectively.Cell survival was measured using CCK8 assay,and proliferation inhibition of the cells after AZD9291 treatment was examined with colony-forming assay;the cell repair and migration abilities were determined using scratch assay and Transwell experiment.The expressions of EGFR-related signaling proteins and migration-related proteins were detected using Western blotting.Results The results of CCK8 assay and colony forming assay showed that AZD9291 significantly inhibited the viability and proliferation of both HNE1 and CNE2Z cells(P<0.01).AZD9291 treatment also attenuated the migration ability of HNE1 and CNE2Z cells(P<0.01).Western blotting showed that,as the concentration of AZD9291 increased,the expression levels of the proteins involved in the PI3K-AKT-mTOR signaling pathway were lowered progressively(P<0.01),resulting in inhibition of migration of HNE1 and CNE2Z cells(P<0.01).Conclusion AZD9291 suppresses proliferation and attenuates repair and migration capacities of nasopharyngeal carcinoma cells by inhibiting the EGFR/PI3K/AKT/mTOR signaling pathway,suggesting the potential value of AZD9291 in the treatment of nasopharyngeal carcinoma.