蛋白激酶B抑制剂增强胃癌细胞对足叶乙甙敏感性的研究  

Protein kinase B inhibitor enhance sensitivity of gastric cancer cell to etoposide

作　　者：徐细明[1] 于红刚[2] 吴耀贵[1] 戈伟[1] 

机构地区：[1]武汉大学人民医院肿瘤中心,430060 [2]武汉大学人民医院消化科,430060

出　　处：《中华胃肠外科杂志》2007年第2期138-142,共5页Chinese Journal of Gastrointestinal Surgery

基　　金：国家自然科学基金资助项目（30300154）

摘　　要：目的观察化疗药物足叶乙甙（etoposide，依托泊甙）对不同分化程度胃癌细胞株蛋白激酶B（PKB）活性的影响及胃癌细胞对其敏感性的变化。探讨PKB活性与胃癌细胞对足叶乙甙敏感性的关系。方法用非放射性蛋白激酶活性分析方法检测胃癌细胞MKN-28（高分化）、SGE-7901（中分化）、BGC-823（低分化）和HGC-27（未分化）基础状态PKB活性，再用足叶乙甙分别作用于经过和未经过Wortmannin预处理的胃癌细胞，检测不同时间点（0、3、6、12和24h）的PKB活性，并采用噻唑蓝（MTT）比色法和流式细胞仪检测细胞不同时间点的生存率和凋亡率。结果分化程度越低的胃癌细胞．PKB活性越强。足叶乙甙作用于未经Wortmannin预处理组胃癌细胞不同时间后，胃癌细胞的PKB活性增强、生存率降低和凋亡率增高，并呈时间依赖性；足叶乙甙作用于经过Wortmannin预处理组胃癌细胞后，未能检出PKB活性表达，SGC-7901、BGC-823和HGC-27细胞生存率降低、凋亡率增高，与未经Wortmannin预处理组相比更加明显。结论足叶乙甙可以诱导胃癌细胞PKB活性的增强．Wortmannin预处理可以有效增强中低分化胃癌细胞对足叶乙甙的敏感性。Objective To observe the effects of etopeside on protein kinase B （PKB） activity in distinct differentiated gastric cancer cell lines and the change of sensitivity to etoposide after pretreatment by wortmannin,a PKB inhibitor. To explore the relationship between PKB activity in gastric cancer cells and their sensitivity to etoposide chemotherapy. Methods Four distinct differentiated gastric cancer cell lines, including MKN-28 （well differentiated）, SGC-7901 （moderate differentiated）, BGC-823 （poorly differentiated） and HGC-27 （undifferentiated）, were studied. The PKB activities of these cell lines were detected by nonradioactive protein-kinase assay at different time points after etoposide treatment for 0,3,6, 12,24 h with or without wortmannin pretreatment. Cell viabilities were assayed by MTr and cell apoptosis was analyzed by flow cytometry. Results Poorer differentiated gastric cancer cell lines had higher PKB activities. Etoposide treatment resulted in increase in PKB activity and apoptosis rate,and decrease in cell survival rate in a time-dependent manner in gastric cancer cell lines. Wortmannin pretreatment abolished PKB activity completely in gastric cancer cells, and decreased survival rate and increased apoptosis rate in SGC-7901 ,BGC-823,and HGC-27 cell lines. Conclusions Etoposide can induce the PKB activity in gastric cancer cell lines. Wortmanin pretreatment enhances sensitivity of median and low differentiated gastric cancer cells to etoposide chemotherapy.

关 键 词：胃肿瘤 蛋白激酶B 依托泊甙 足叶乙甙 药物敏感性 

分 类 号：R735[医药卫生—肿瘤]