ERK1/2介导的bFGF对肝癌细胞系Bel-7402细胞增殖和凋亡的影响  

Effects of bFGF on proliferation and apoptosis in liver carcinoma cell line Bel-7402 via ERK1/2 pathway

作　　者：刘萍[1] 孙黎光[1] 侯伟健[1] 于卉影[2] 

机构地区：[1]中国医科大学基础医学院生物化学与分子生物学教研室,辽宁沈阳110001 [2]沈阳军区总医院医学实验科

出　　处：《中国医科大学学报》2006年第5期451-453,共3页Journal of China Medical University

基　　金：国家自然科学基金资助项目(39870384)

摘　　要：目的:观察Ras-Raf-ERK1/2途径介导的碱性成纤维细胞生长因子(bFGF)对肝癌细胞系Bel-7402细胞增殖和凋亡的影响,探讨bFGF及其信号转导途径与肝癌发生发展的关系。方法:以bFGF和PD98059处理Bel-7402细胞,流式细胞术检测细胞周期与凋亡情况;MTT法检测细胞增殖情况;Western blot检测细胞外信号调节蛋白激酶(ERK1/2)的活化。结果:bFGF处理,诱导细胞进入S期[S期细胞比例(27.49±0.72)%→(42.45±1.06)%];细胞增殖比明显增加,且与bFGF水平成剂量依赖关系,bFGF浓度为25 ng/ml时细胞增殖比最高为129%;使无血清饥饿诱导的凋亡细胞比例下降[(28.89±3.13)%(→1.70±2.10)%];时、量效依赖性地诱导ERK1/2活性增高。ERK激活性蛋白激酶(MEK1)抑制剂PD98059可抑制bFGF的这些作用。结论:bFGF通过Ras-Raf-ERK1/2途径介导,加速肝癌Bel-7402细胞的细胞周期进程,促进细胞增殖,抵抗无血清饥饿诱导的凋亡。在肝癌发生发展过程中,bFGF信号传递发挥了重要的作用。Objective： To investigate the effect of basic fibroblast growth factor （bFGF） on the profiferation and apoptosis in hver carcinoma cell line Bel-7402 via Ras-Raf-ERK1/2 pathway, and to study the relationship between signal transduction mechanism of bFGF and the development of hver carcinoma. Methods： The Bel-7402 cell fine was treated with bFGF alone （bFGF group） and bFGF and PD98059 （PD98059＋bFGF group）, respectively. The cell cycle distribution and apoptosis rate, proliferation rate, and ERK1/2 activity of Bel-7402 cell hne were determined by flow cytometry, MTT assay, and Western blot, respectively. Results： bFGF induced S-phase entry, and the percentage of cell in S-phase in bFGF group was significantly higher than that in control group （42.45±1.06% vs. 27.49±0.72%）. bFGF increased the proliferation of Bel-7402 cell hne in a dose-dependent manner, and the proliferation rate increased to 129% when the cell fine was treated with 25 ng/ml bFGF. Induced by starvation, the apoptosis rate of Bel-7402 cell fine in bFGF group was significantly lower than that in control group （1.70±2.10% vs. 28.89±3.13%）. bFGF increased ERK1/2 activity in a time- and dose-dependent manner. All these effects of bFGF mentioned above were inhibited by PD98059, the MEK1 inhibitor. Conclusion：In fiver carcinoma cell line Bel- 7402, bFGF could promote the cell cycle, increase the profiferation rate, and decrease apoptosis rate via Ras-Raf-ERK1/2 pathway, bFGF signal transduction may play important roles in the development of fiver carcinoma.

关 键 词：肝癌 碱性成纤维细胞生长因子 细胞外信号调节蛋白激酶 增殖 凋亡 

分 类 号：R735.7[医药卫生—肿瘤]