香叶木素通过调控p38JNK信号通路对鼻咽癌CNE2细胞凋亡和增殖的影响

Effect of Diosmetin on Apoptosis and Proliferation of Nasopharyngeal Carcinoma CNE2 Cells by Regulating the p38JNK Signal Pathway

目的观察香叶木素在体外对鼻咽癌CNE2细胞凋亡和增殖的影响,并探讨其作用机制。方法应用不同浓度香叶木素处理的人鼻咽癌CNE2细胞作为实验组,加入药物溶解介质的人鼻咽癌CNE2细胞作为对照组。MTT法检测鼻咽癌CNE2细胞的生长抑制情况,流式细胞仪检测细胞凋亡情况以及香叶木素对鼻咽癌CNE2细胞周期的影响,Western Blotting方法检测p38JNK信号通路蛋白表达情况。结果不同浓度的香叶木素对鼻咽癌CNE2细胞具有抑制生长和提高凋亡率作用,且随着香叶木素浓度的上升,细胞生长抑制率和凋亡率均逐渐上升,呈现浓度依赖性(P<0.05)。与孵育0 h组比较,香叶木素可使鼻咽癌CNE2细胞G1期细胞比例显著减少,而在G2/M期细胞比例显著增加,且随着香叶木素孵育时间的延长,G1期细胞比例逐渐减少,G2/M期细胞比例逐渐增加(P<0.05)。不同浓度香叶木素对鼻咽癌CNE2细胞磷酸化Erkl/2蛋白表达无明显影响(P>0.05);随着香叶木素浓度的增加,p38蛋白和JNK蛋白含量的表达均呈现上升趋势,且呈现浓度依赖性(P<0.01)。结论香叶木素可促进鼻咽癌CNE2细胞凋亡,通过改变其细胞周期抑制增殖,作用机制可能与引起细胞G2/M期阻滞和活化p38JNK信号通路有关。

Objective To observe the effect of Diosmetin on apoptosis and proliferation of nasopharyngeal carcinoma CNE2 in vitro,and to further explore its mechanism of action.Methods The nasopharyngeal carcinoma CNE2 cells treated with different concentrations of Diosmetin were used as the experimental group,and nasopharyngeal carcinoma CNE2 cells supplemented with the drug dissolution medium were used as the control group.MTT method was used to detect the growth inhibition of nasopharyngeal carcinoma CNE2 cells.Flow cytometry was used to detect the apoptosis and to detect the effect of Diosmetin on cycle of nasopharyngeal carcinoma CNE2 cells.Western Blotting method was used to detect the expression of p38JNK signal transduction pathway protein.Results Different concentrations of Diosmetin could inhibit the growth and increase the apoptosis rate of CNE2 cells of nasopharyngeal carcinoma.With the increase in the concentration of Diosmetin,the cell inhibition rate and apoptosis rate were gradually increased in a concentration-dependent manner(P<0.05).Compared with that in the incubation for 0 h group,Diosmetin could significantly reduce the proportion of nasopharyngeal carcinoma CNE2 cells at G1 phase,while the proportion of cells at G2/M phase was increased significantly.With the extension of incubation time in Diosmetin,the proportion of cells in G1 phase was gradually decreased,and the proportion of cells in G2/M phase was gradually increased(P<0.05).The different concentrations of Diosmetin had no significant effect on the expression of phosphorylated Erkl/2 protein in nasopharyngeal carcinoma CNE2 cells(P>0.05).With the increasing of concentration,the expressions of p38 protein and JNK protein both showed an upward trend in a concentration-dependent manner(P<0.01).Conclusion Diosmetin can promote the apoptosis of nasopharyngeal carcinoma CNE2 cells,and inhibit its proliferation by changing the cell cycle.The mechanism may be related to the p38JNK signal pathway that causes cells to block and activate in the G2/M phase.