吉非替尼与TRAIL协同诱导A549人肺腺癌细胞系凋亡的作用研究

Study on the Synergistic Effects on the Induction of Apoptosis in A549 Human Lung Adenocarcinoma Cell Line by Gefitinib and TRAIL

目的:本论文旨在探讨吉非替尼与肿瘤坏死因子相关凋亡诱导配体TRAIL (TNF-Related Apoptosis Inducing Ligand)的协同抗人肺癌作用并阐明两者协同的机制。方法:实验采用人A549肺癌细胞。实验分为对照组、吉非替尼处理组、TRAIL处理组及吉非替尼和TRAIL共同处理组。分别采用MTT实验,流式细胞术,Western-blot检测吉非替尼和TRAIL对A549细胞的存活、凋亡以及凋亡相关蛋白等方面的影响。结果:吉非替尼和TRAIL共同处理组的细胞存活率相较于空白对照组和各单独处理组均有显著变化。流式细胞术检测结果显示:对照组诱导的A549细胞凋亡比率分别为2.7%,15 μM吉非替尼单独处理组诱导的凋亡率为8.5%,100 ng/ml TRAIL单独处理组诱导的凋亡率为17.5%,而两者共同处理组诱导的凋亡比例为69.8%。相较与对照组或各单独处理组都有显著升高(P < 0.01)。Western-blot实验结果表明:吉非替尼和TRAIL显著诱导凋亡相关蛋白的水解。结论:吉非替尼和TRAIL可协同抑制肺癌细胞存活,促进细胞凋亡。

Objective: This paper aims to explore the synergistic anti-lung cancer effect of gefitinib and TRAIL (TNF-Related Apoptosis Inducing Ligand), and elucidate the mechanism of their synergy. Method: The experiment applied human A549 lung cancer cells. The experiment was divided into control group, gefitinib treatment group, TRAIL treatment group, and gefitinib and TRAIL co-treatment group. MTT assay, flow cytometry, and Western-blot were used to detect the effects of gefitinib and TRAIL on the cell viability, apoptosis, and apoptosis related proteins of A549 cells. Result: The cell viability of the co-treated group with gefitinib and TRAIL showed significant changes compared to the control group and each individual treatment group. The results of flow cytometry showed that the apoptosis ratio of A549 cells induced by the control group were 2.7%. The apoptosis induced by 15 μM of gefitinib alone treatment group was 8.5%, the apoptosis induced by 100 ng/ml TRAIL alone treatment group was 17.5%, and the apoptosis induced by the combined treatment group was 69.8%. Compared with the control group or each individual treatment group, there was a sig-nificant increase (P < 0.01). The Western-blot experiment results showed that gefitinib and TRAIL significantly induced the hydrolysis of apoptosis related proteins. Conclusion: Gefitinib and TRAIL can synergistically inhibit the viability of lung cancer cells and promote cell apoptosis.