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目的评价酪氨酸激酶受体抑制剂AL3810对人肺腺癌细胞A549的体外及体内抗肿瘤作用。方法①采用MTT法评价AL3810对13种人体肿瘤细胞株和人胚肺细胞的体外增殖抑制作用。②采用流式细胞仪检测AL3810诱导细胞凋亡的能力及其对细胞周期的影响。③采用流式细胞仪检测AL3810诱导Caspase-3活化的作用。④划痕试验评价AL3810对A549细胞体外迁移的影响。⑤以人肺腺癌A549裸鼠异种移植瘤模型评价AL3810对肿瘤生长抑制作用的量效关系。结果AL3810对大部分细胞均有很强的生长抑制作用。其能诱导A549细胞凋亡且具有时效性,能将细胞周期阻滞于G0-G1期;能将无活性的Caspase-3前体活化且具有时效关系;能时间依赖性地显著抑制A549细胞的体外迁移;对A549异种移植瘤生长具有良好的抑制作用,且具有量效关系。结论酪氨酸激酶受体抑制剂AL3810具有显著的抗肿瘤活性,能剂量依赖性地抑制A549的生长。可能机制为诱导肿瘤细胞凋亡和阻滞细胞周期于G0-G1期、诱导细胞内Caspase-3活化、抑制细胞迁移等,值得进一步开发。
Objective To evaluate the antitumor effect of tyrosine kinase receptor inhibitor AL3810 on human lung adenocarcinoma cell line A549 in vitro and in vivo. Methods ① MTT assay was used to evaluate the inhibitory effect of AL3810 on the proliferation of 13 kinds of human tumor cell lines and human embryonic lung cells in vitro. ② The ability of AL3810 to induce apoptosis and its effect on cell cycle were detected by flow cytometry. ③ using flow cytometry AL3810-induced Caspase-3 activation. ④ scratch test evaluation of AL3810 on A549 cell migration in vitro. ⑤ Human lung adenocarcinoma A549 xenograft model in nude mice to evaluate the dose-effect relationship of AL3810 on tumor growth inhibition. Results AL3810 had a strong growth inhibitory effect on most of the cells. It can induce apoptosis of A549 cells and has timeliness, can arrest the cell cycle in the G0-G1 phase; can activate the inactive Caspase-3 precursor and has an aging relationship; a significant time-dependent inhibition of A549 cells Migration in vitro; A549 xenograft tumor growth has a good inhibitory effect, and has a dose-response relationship. Conclusion The tyrosine kinase receptor inhibitor AL3810 has significant anti-tumor activity and inhibits the growth of A549 in a dose-dependent manner. Possible mechanism is to induce tumor cell apoptosis and arrest the cell cycle in the G0-G1 phase, induce intracellular Caspase-3 activation, inhibit cell migration, worth further development.