榄香烯和PD98059诱导人胃癌SCG-7901细胞株凋亡及其机制的探讨

目的：探讨榄香烯及PD98059对人胃癌SCG-7901细胞株凋亡的影响，及其与ERK1／2、P38MAPK信号通路的关系。方法：用不同浓度的榄香烯和PD98059处理人胃癌SCG-7901细胞，体外细胞增殖抑制实验（MTT）法检测细胞增殖情况；Western—blot法检测ERKl／2、磷酸化ERKl／2（p-ERK1／2）和磷酸化P38（p-P38）的表达；RT-PCR检测bcl-2mRNA及baxmRNA的表达；TUNEL法检测胃癌细胞凋亡并计算凋亡指数。结果：榄香烯和PD98059单独作用都有抑制胃癌细胞增殖的作用，前者呈浓度和时间依赖性，后者则呈时间依赖性但无浓度依赖性，两药联合作用时对胃癌细胞增殖的抑制作用显著大于单一用药时（P〈0．05）；随榄香烯的浓度增加p-ERK1／2蛋白的表达量增加（P〈0．05），总FRK1／2无明显变化；榄香烯（0．08mg／mL）、PD98059（50μmol／L）及榄香烯＋PD98059组作用胃癌细胞24h，p-P38的表达均高于对照组（P〈0．05），且榄香烯＋PD98059组较榄香烯组或PD98059组更高（P〈0．05）；随榄香烯浓度的增加，baxmRNA的表达增加，bcl-2mRNA的表达降低，且榄香烯＋PD98059组表现最显著；实验组细胞凋亡率均高于对照组（P〈0．05），具有浓度依赖性（P〈0．05），且榄香烯＋PD98059组的凋亡率明显高于单一作用组（P〈0．05）。结论：榄香烯及PD98059可以抑制胃癌细胞增殖，前者具有时间和浓度依赖性；榄香烯及PD98059还可以促进胃癌细胞凋亡。榄香烯抑制细胞增殖、促进细胞凋亡的机制包括促进ERKl／2磷酸化和上调P-P38MAPK信号通路的表达；PD98059抑制ERKl／2的磷酸化，但通过上调p-P38MAPK信号通路的表达而发挥其细胞调节作用。

The mechanism of elemene and PD98059 inducing apoptosis of human gastric cancer cell line SCG- 7901

Objective： To explore the effect of elemene and PD98059 on the apoptosis of human gastric cancer cell line SGC-7901 and the relationship of ERK1/2, P38MAPK signal pathway. Methods： SGC-7901 cells were treated with elemene and PD98059. MTT assay was used to detect the proliferation of SGC-7901 cells. The expression of ERKI/2, phosphorylation REKI/2 （p-ERKI/2） and phosphorylated P38 （p-P38） was detected by western-blot.The bcl-2 mRNA and bax mRNA was detected with RT-PCR. The gastric cancer cell apoptosis index was detected by TUNEL method. Results： Elemene and PD98059 alone effectively inhibited the proliferation of gastric cancer cells SGC-7901, and the former was in a dose-dependent and time-dependent manner, the latter was in a time-dependence but no in dose-dependent manner, and the combined effects of the two drugs on gastric cancer cell proliferation inhibition was significantly greater than that of single agent （P〈0.05）. The expression of p-ERK 1/2 protein was increased （P〈0.05）, and the total ERK1/2 was no significant change with the concentration of elemene increased. The expression of p-P38 of elemene group, PD98059 group and the combined group were significantly higher than that of the control group （P〈0.05）, and the combined group was the highest （P〈0.05）. The mRNA of bcl-2 expression was down-regulated while the expression of bax mRNA was up-regulated and both changes had good dose-dependent tendency, and the combined group was most significantly. Cell in experimental groupsapoptosis rate was higher than that in the control group （P〈0.05）, and in a dose-dependent manner with elemene （P〈0.05）.The apoptosis rate of elemene＋PD98059 group was significantly higher than that of the single-action group （P〈0.05）. Conclusion： Elemene and PD98059 can inhibite the proliferation of gastric cancer cells SGC- 7901, and the former was in a dose-dependent and time-dependent manner. Elemene and PD98059 can also promote the apoptosis of gastric cancer cells. Elemene promotes apoptosis and inhibites the proliferation of gastric cancer cells by up-regulating the expression of p-ERK1/2 signaling pathway and p-P38MAPK signaling pathway. PD98059 inhibites the ERK1/2 phosphorylation, but can promote the expression of p-P38 MAPK signaling pathway, then inhibites the proliferation and promotes gastric cancer cell apoptosis.