青蒿琥酯联合奥沙利铂诱导胃癌细胞凋亡及对p38MAPK和Caspase-3表达的影响  

Artesunate combined with oxaliplatin inhibits proliferation and induces apoptosis of human gastric cancer SGC-7901 cells

作　　者：周磊[1] 葛小刚[1] 林赛锋[1] 孙维建[1] 李丕宏[1] 郑志强[1] 

机构地区：[1]温州医学院附属第二医院胃肠外科,325027`

出　　处：《浙江医学》2012年第5期313-316,322,397,共6页Zhejiang Medical Journal

摘　　要：目的观察青蒿琥酯联合奥沙利铂对胃癌细胞SGC-7901生长的抑制作用，并探讨其可能的机制。方法应用光学显微镜观察青蒿琥酯联合奥沙利铂对胃癌细胞形态学变化的影响；噻唑氮蓝（MTT），吖啶橙／溴化乙锭（AO／EB）双荧光染色法检测细胞活力及细胞凋亡情况；RT-PCR及Westernblot检测p38丝裂原活化蛋白激酶（p38MAPK）及半胱氨酸天冬氨酸特异性蛋白酶-3（Caspase-3）表达水平。结果（1）青蒿琥酯及奥沙利铂单独作用胃癌细胞后，其生长均明显被抑制，抑制率具有浓度依赖性（P〈0．05）。（2）青蒿琥酯联合奥沙利铂对胃癌细胞的抑制率优于青蒿琥酯或奥沙利铂单药使用，两者具有协同作用。（3）胃癌细胞的凋亡率随药物作用浓度增加而增加。（4）青蒿琥酯及青蒿琥酯联合奥沙利铂作用于胃癌细胞后p38MAPK、Caspase-3表达量均明显增加（均P〈005）。结论青蒿琥酯联合奥沙利铂能有效抑制胃癌细胞增殖，诱导其凋亡。其机制可能是通过p38MAPK通路诱导p38MAPK和Caspase-3表达增加最终导致胃癌细胞凋亡有关。Objective To investigate the effect of artesunate combined with oxaliplatin on proliferation and apoptosis of human gastric cancer cell line SGC-7901 and its mechanism. Methods SGC-7901 cells were treated with different concentra- tions of artesunate combined with oxaliplatin in vitro. The proliferation of SGC-7901 cells was measured by MTT method and cell apoptosis was detected by acridine orange/ethidium bromide fluorescent staining. The expression of p38MAPK and Caspase-3 mRNA and protein in SGC-7901 cells was assessed by reverse transcriptase polymerase chain reaction （RT-PCR） and Western blot, respectively. Results Artesunate alone and artesunate combine with oxaliplatin effectively inhibited proliferation of SGC7901 cells in a dose-dependent manner（P〈0.05）; the effects with combination of two drug were more markedly than those of single drug. Apoptosis was observed by optical microscope and acridine orange/ethidium bromide fluorescent staining, the effect was in a dose-dependent manner. RT-PCR and WB revealed that the expression of p38MAPK and Caspase-3 was in- creased after treatment of artesunate or artesunate with oxaliplatin （P〈0.05）. Conclusion Artesunate combined with oxaliplatin can effectively inhibit the proliferation and induce apoptosis in SGC-7901 cells, which may be related to the up-regulation of p38MAPK and Caspase-3.

关 键 词：胃癌 凋亡 青蒿琥酯 P38丝裂原活化蛋白激酶 半胱氨酸天冬氨酸特异性蛋白酶-3 

分 类 号：R651.15[医药卫生—外科学]