雷帕霉素介导丝裂原活化蛋白激酶信号通路对肝癌细胞的影响  

Effects of rapamycin mediated mitogen-activated protein kinase signaling pathway on hepatocellular carcinoma cells

作　　者：巩江 贺学[1] 沙莎 戎浩 倪士峰[2] Gong Jiang;He Xue;Sha Sha;Rong Hao;Ni Shifeng(Medical College,Xizang Minzu University,Xianyang 712082;Department of Traditional Chinese Medicine,Northwestern Polytechnical College,Xi’an 710000,China)

机构地区：[1]西藏民族大学医学院,咸阳712082 [2]西北大学生科院中药系,西安710000

出　　处：《解剖学杂志》2021年第4期307-311,共5页Chinese Journal of Anatomy

摘　　要：目的:探讨雷帕霉素介导丝裂原活化蛋白激酶(MAPK)信号通路对肝癌细胞Bcl-2、Bcl-xl及Bax蛋白表达的影响。方法:将人肝癌细胞BEL-7402细胞分为对照组和雷帕霉素处理组(20、50、100 ng/mL),观察各组BEL-7402细胞的形态变化、细胞增殖抑制率、凋亡及蛋白(MAPK、Bcl-2、Bcl-xl及Bax)表达。结果:随着雷帕霉素浓度的升高,BEL-7402细胞呈现崩解和坏死;对照组BEL-7402细胞增殖抑制率最低,雷帕霉素干预组BEL-7402细胞增殖抑制率高于对照组,随着时间及雷帕霉素浓度的升高,细胞生长抑制率逐渐升高;雷帕霉素处理组与对照组相比差异有统计学意义;随着浓度的升高,BEL-7402细胞凋亡率升高;对照组BEL-7402细胞中MAPK阳性表达率高于雷帕霉素处理组,雷帕霉素处理组随着浓度升高,MAPK阳性表达率不断降低;对照组BEL-7402细胞中Bcl-2、Bcl-xl蛋白升高,与雷帕霉素处理组比较存在显著差异,雷帕霉素处理组Bcl-2、Bcl-xl蛋白水平随着雷帕霉素的浓度升高而降低,Bax表达水平随着雷帕霉素的浓度升高而增加。结论:雷帕霉素能够抑制肝癌细胞增殖,加快坏死及破裂,随着雷帕霉素的浓度升高,凋亡程度增大,其作用机制可能与抑制MAPK、Bcl-2、Bcl-xl表达,促进Bax水平升高有关。Objective:To investigate the effects of rapamycin mediated mitogen-activated protein kinase(MAPK)signaling pathway on the protein expressions of Bcl-2,Bcl-xl,and Bax in hepatoma cells.Methods:Human hepatocellular carcinoma BEL-7402 cells were divided into control group and rapamycin(RAPA)-treated group(20,50,100 ng/mL).Morphological changes,cell proliferation inhibition rate,apoptosis,and protein expression(MAPK,Bcl-2,Bcl-xl and Bax)of BEL-7402 cells in each group were observed.Results:BEL-7402 cells showed disintegration and necrosis with the increase of RAPA concentration.The inhibitory rate of BEL-7402 cell proliferation in the control group was the lowest,and that in the RAPA treatment group was higher than that in the control group.With the increase of time and RAPA concentration,the inhibitory rate of BEL-7402 cell growth was gradually increased.The RAPA treatment group had statistical significance compared with the control group.With the increase of concentration,the apoptosis rate of BEL-7402 cells increased.The positive expression rate of MAPK in BEL-7402 cells in control group was higher than that in RAPA treatment group,and the positive expression rate of MAPK in RAPA treatment group was decreased continuously under the intervention of multiple concentrations of RAPA.The protein levels of Bcl-2 and Bcl-xl in BEL-7402 cells in control group were increased,which were different from those in RAPA group.The protein levels of Bcl-2 and Bcl-xl in RAPA group were decreased with the increase of rapamycin concentration.The expression level of Bax increased with the increase of rapamycin concentration.Conclusion:RAPA can inhibit the proliferation of liver cancer cells and accelerate necrosis and rupture.With the increase of RAPA concentration,the degree of apoptosis increases,and its mechanism may be related to the inhibition of MAPK,Bcl-2,Bcl-xl expression and promotion of Bax levels.

关 键 词：雷帕霉素 人肝癌细胞(BEL-7402细胞) 丝裂原活化蛋白激酶 Bcl-2 BCL-XL Bax 

分 类 号：R735.7[医药卫生—肿瘤]