新型TK抑制剂达克替尼在肺腺癌细胞增殖和凋亡的影响

Effect of a Novel TK Inhibitor Dacomitinib on Proliferation and Apoptosis of Lung Adenocarcinoma Cells

目的:探究新型TK抑制剂达克替尼对人肺腺癌A549细胞增殖与侵袭作用及机制。方法:人肺腺癌A549细胞为研究对象,根据预实验结果,将人肺腺癌细胞系A549分成3组,即空白对照组,低剂量组和高剂量组。RT-PCR检测EFGR和凋亡蛋白Caspase-3和Caspase-9的表达,流式细胞仪检测细胞的分裂周期和细胞凋亡率,CCK-8检测细胞的增殖。结果:空白对照组,低剂量组和高剂量组的EFGR,Caspase-3和Caspase-9 mRNA相对表达量相对量比较具有统计学差异(P 0.05)。低剂量组和高剂量组的G0/G1期比例明显高于空白对照组(P 【0.05);S期和G2期比例明显低于空白对照组(P 【0.05)。低剂量组和高剂量组的总凋亡率明显高于空白对照组(P 【0.05);高剂量组晚期凋亡率明显高于低剂量组(P 【0.05)。药物处理2天后,空白对照组的细胞增值率要明显高于低剂量组和高剂量组(P 【0.05);药物处理3天后,空白对照组的细胞增值率要明显高于低剂量组和高剂量组(P 【0.05)。结论:低剂量达克替尼可以抑制肺腺癌细胞的增殖,促进肺腺癌细胞的凋亡,并且可以抑制EFGR的表达,可以作为耐药性肺腺癌的治疗方案。

Objective: The objective is to investigate the proliferation and invasion of human lung adenocar-cinoma A549 cells induced by a novel TK inhibitor, dacomitinib, and its mechanism. Methods: Human lung adenocarcinoma cell line A549 was divided into three groups according to the pre-liminary results, namely the blank control group, the low-dose group and the high-dose group. The expression of EFGR and Caspase-3 and Caspase-9 was detected by RT-PCR. The cycle of cell division and apoptotic rate of the cell were detected by flow cytometry. The cell proliferation was detected by CCK-8. Results: The relative expressions of EFGR, caspase-3 and caspase-9 mRNA in blank control group, low-dose group and high-dose group were statistically different (P 0.05). The proportions of G0/G1 phase in low-dose group and high-dose group were significantly higher than those in blank control group (P 0.05). The proportions of G0/G1 phase in low-dose group and high-dose group were significantly higher than those in blank control group (P <0.05), while the proportions of S phase and G2 phase were significantly lower than those in blank control group (P <0.05). The total apoptotic rate of the low-dose group and the high-dose group significantly higher than that of the blank control group (P <0.05), and the late apoptotic rate of the high-dose group was significantly higher than that of the low-dose group (P <0.05). After 2 days of drug treatment, the cell increment rate of blank control group was signifi-cantly higher than that of low-dose group and high-dose group (P <0.05);after 3 days of drug treatment, the cell increment rate of blank control group was significantly higher than that of low-dose group and high-dose group (P <0.05). Conclusion: Low-dose of dacomitinib can inhibit the proliferation of lung adenocarcinoma cells, promote the apoptosis of lung adenocarcinoma cells, and inhibit the expression of EFGR. It can be used as a therapeutic regimen for drug-resistant lung ade-nocarcinoma.