抑制ERK通路增强苦参碱诱导的肝癌HepG2细胞凋亡  

Inhibition of ERK Signal Pathway Enhances Matrine-Induced Apoptosis in Human HepG2 Cells

作　　者：何星星[1] 谢步善[1] HE Xingxing;XIE Bu shan(Department of Gastroenterology,the First Affiliated Hospital ofNanchang University,Nanchang 330006,Chin)

机构地区：[1]南昌大学第一附属医院消化内科,南昌330006

出　　处：《南昌大学学报（医学版）》2018年第3期1-4,107,共5页Journal of Nanchang University：Medical Sciences

基　　金：国家自然科学基金(81503437);江西省自然科学基金(20161BAB205246);江西省卫生计生委中医药科研课题(2015B024)

摘　　要：目的探讨苦参碱诱导肝癌细胞凋亡的作用和分子机制。方法体外培养人肝癌细胞株HepG2,不同质量浓度(0、0.8、1.6和2.4mg·mL-1)苦参碱处理HepG2细胞48h,流式细胞术和显微镜观察细胞凋亡的变化;western blot检测0和1.6mg·mL-1苦参碱处理HepG2细胞48h后p-ERK蛋白的表达;以DMSO处理细胞作为对照,1.6mg·mL-1苦参碱加或不加U0126处理HepG2细胞48h,流式细胞术和显微镜观察细胞凋亡的变化。结果苦参碱诱导细胞出现典型的凋亡形态学变化,其中1.6和2.4 mg·mL-1苦参碱组细胞凋亡率显著高于对照组即0mg·mL-1苦参碱组(29.7%和43.3%比6.7%,P<0.01),而0.8mg·mL-1苦参碱组细胞凋亡率与对照组比较差异无统计学意义(11.1%比6.7%,P=0.16),故后续实验选择1.6 mg·mL-1苦参碱处理细胞;1.6 mg·mL-1苦参碱组较对照组显著抑制p-ERK蛋白的表达;1.6 mg·mL-1苦参碱联合U0126处理组细胞凋亡率显著高于苦参碱单用药组(63.3%比30.4%,P<0.05)。结论苦参碱能诱导肝癌细胞凋亡,其机制可能与负向调控ERK信号通路有关。ObjectiveTo investigate the effect of matrine on hepatocellular carcinoma cell apoptosis and its molecular mechanisms of action. Methods The cultured human hepatocellular carcinoma cells（HepG2） were treated with different concentrations of matrine（0.8,1.6 and 2.4 mg·mL^ -1 ） for 48 hours.Control cells only received DMSO vehicle.The apoptosis was detected by microscopy and flow cytometry.The expression of p-ERK was measured by Western blot.In addition,the apoptosis of HepG2 cells was observed after treatment with 1.6 mg·mL^-1 matrine alone or in combination with U0126 for 48 hours. Results HepG2 cells displayed typical apoptotic morphology after treatment with matrine.The apoptosis rate in 1.6 mg·mL^-1 treatment group（29.7%） or 2.4 mg·mL^-1 treatment group（43.3%） was significantly higher than that in control group（6.7%）（ P 〈0.01）.However,the difference in apoptosis rate was not significant between 0.8 mg· mL^-1 treatment group and control group（11.1% vs 6.7%, P =0.16）.Compared with control group,treatment with 1.6 mg·mL^-1 matrine obviously inhibited the expression of p-ERK protein.Compared with treatment with 1.6 mg·mL^-1 matrine alone,the apoptosis rate was markedly increased by combined treatment with U0126（63.3% vs 30.4%, P 〈0.05）. Conclusion Matrine induces hepatocellular carcinoma cell apoptosis by negatively regulating ERK signal pathway.

关 键 词：肝癌 细胞凋亡 苦参碱 ERK信号通路 机制 

分 类 号：R285.5[医药卫生—中药学] R735.7[医药卫生—中医学]