紫杉醇对肺腺癌A549细胞株增殖和凋亡的影响

Effects of Paclitaxel on Cell Proliferation and Apoptosis of Human Lung Adenocarcinoma A549 Cells

目的:探讨紫杉醇在体外对肺腺癌A549细胞株增殖和凋亡的影响及其作用机制。方法:采用MTT法测定紫杉醇对A549细胞增殖的影响;Hoechst33258检测紫杉醇作用48h后细胞凋亡情况;流式细胞仪检测药物作用48h后的细胞周期和凋亡率;Western Blot检测的Bax和Bcl-2蛋白的表达。结果:紫杉醇抑制A549细胞增殖呈时效和量效关系;Hoechst33258检测紫杉醇作用48h后可见凋亡细胞;紫杉醇作用48h后药物组G2～M期细胞百分比均高于对照组(均P<0.01),药物组细胞凋亡率高于对照组(均P<0.01),且凋亡率随药物浓度增加而增加;Western Blot显示,不同浓度紫杉醇作用于A549细胞48h,Bax的表达随药物浓度增加而增加,Bcl-2的表达随药物浓度增加而减低。结论:紫杉醇能抑制肺腺癌A549细胞株的增殖,其抑制作用可能通过将细胞周期阻滞于G2～M期和通过上调Bax、下调Bcl-2的表达而诱导细胞凋亡来实现的,并且紫杉醇抑制A549细胞增殖和诱导凋亡作用随药物浓度增加而增加。

Objective： To investigate the effects of paclitaxel on cell proliferation and apoptosis of human lung adenocarcinoma A549 cells line and its mechanism in vitro. Methods： Cell growth inhibition of paclitaxel on A549 cells was analyzed by MTT assay. Cell apoptosis was detected by Hoechst 33258 staining after paclitaxel treatment for 48 hours. Cell cycle and apoptotic rate were analyzed by cytometry. Protein expressions of Bax and Bcl-2 were studied by Western Blot. Results： Paclitaxel could inhibit the proliferation of A549 cells in a time-and dose-dependant manner. Hoechst 33258 staining indicated that apoptosis was induced by paclitaxel. After treated for 48 hours,G2 -M stage cell percentage of paclitaxel groups were significantly higher than that of control group（P 〈 0.01 ）. Cell apoptosis rate of paclitaxel groups were significantly higher than that of control group（P 〈 0.01 ）. And apoptosis rate increased in dose-dependant manner. Western blot showed that paclitaxel increased protein express of Bax and decreased protein express of Bcl-2 in a dose-dependant manner. Conclusion： Paclitaxel can inhibit A549 cells proliferation in a time- and dose-dependant manner. The mechanism may be to arrest cell cycle in G2 -M stage and induce cell apoptosis by upmodulating Bax expression and downmodulating Bcl-2 expression.