阿美替尼对结肠癌细胞增殖、迁移侵袭及凋亡的抑制作用

Inhibitive Effect of Almonertinib on Proliferation,Invasion,Migration and Apoptosis of Colon Cancer Cells

目的探究表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKI)阿美替尼对结肠癌SW620、HT29细胞增殖、侵袭迁移和凋亡的作用及机制。方法体外培养结肠癌SW620、HT29细胞,CCK-8法、流式细胞术、Transwell实验检测阿美替尼对SW620、HT29细胞增殖、凋亡、侵袭及迁移的影响;Western blot实验检测凋亡和侵袭迁移相关蛋白Bax、Bcl-2、E-Cadherin、Vimentin的表达。将SW620细胞注射到5周龄BALB/c裸鼠右前肢皮下,建立裸鼠皮下瘤动物模型,测量皮下瘤体积,记录裸鼠体重、生存曲线,苏木精-伊红(HE)染色观察阿美替尼对心、肝、脾、肺、肾有无损伤作用。结果CCK-8实验表明阿美替尼抑制SW620、HT29细胞增殖;流式细胞术结果表明阿美替尼诱导SW620、HT29细胞发生凋亡;Transwell实验结果表明阿美替尼抑制SW620、HT29细胞侵袭迁移能力;Western blot实验结果表明阿美替尼处理组SW620和HT29细胞中E-Cadherin、Bax蛋白上调,Bcl-2、Vimentin蛋白下调。体内实验结果表明阿美替尼可以对结肠癌细胞皮下移植瘤产生抑制作用,延缓裸鼠体重的减轻,延长荷瘤裸鼠生存时间,HE染色结果表明阿美替尼没有明显的器官毒性。结论阿美替尼能够抑制结肠癌SW620、HT29细胞的增殖、侵袭迁移并诱导SW620、HT29细胞凋亡。

Objective To explore the effect of Almonertinib,an epidermal growth factor receptor-tyrosine kinase inhibitor(EGFR-TKI),on proliferation,invasion,migration and apoptosis of colon cancer cells SW620 and HT29.Methods SW620 and HT29 cells were cultured and treated with Almonertinib.CCK-8 assay,flow cytometry and Transwell assay were used to measure the effects of Almonertinib on the proliferation,apoptosis,invasion and migration of SW620 and HT29 cells.Western blotting was used to evaluate the expression levels of Bax,Bcl-2,E-cadherin and Vimentin.SW620 cells were injected subcutaneously into the right forelimbs of 5-week BALB/c nude mice to establish subcutaneous tumor models in nude mice.The volume of subcutaneous tumor was detected,the body weight and the survival curve of nude mice were recorded.Hematoxylin-eosin(HE)staining was used to observe the damage of heart,liver,spleen,lung and kidney induced by Almonertinib.Results CCK-8 results showed that Almonertinib inhibited the proliferation of SW620 and HT29 cells.Flow cytometry results showed that Almonertinib induced the apoptosis of SW620 and HT29 cells.Transwell assay result showed that Almonertinib inhibited the invasion and migration of SW620 and HT29 cells.Western blotting result showed that Almonertinib upregulated the expression of E-cadherin and Bax while downregulated the expression of Bcl-2 and Vimentin.In vivo experiments showed that Almonertinib had an inhibitive effect on the subcutaneous tumor of colon cancer,delayed the weight loss while prolonged the survival time of tumor-bearing nude mice.HE staining showed that Almonertinib had no obvious toxicity.Conclusion Almonertinib can inhibit the proliferation,invasion and migration of SW620 and HT29 cells,and induce the apoptosis of SW620 and HT29 cells.