硒代胱氨酸协同增敏顺铂诱导人子宫颈癌HeLa细胞凋亡  

Selenocystine sensitizes cisplatin-induced apoptosis of human cervical cancer He La cells

作　　者：袁启霞[1] 张毅芳[2] 范丰田 王琨[3] 

机构地区：[1]日照中医医院妇科,山东日照276800 [2]泰山医学院附属医院妇科,山东泰安271000 [3]泰山护理职业学院教务处,山东泰安271000

出　　处：《实用肿瘤杂志》2015年第4期330-334,共5页Journal of Practical Oncology

基　　金：吴阶平医学基金会临床科研专项资助基金(320.6750.09168)

摘　　要：目的探讨硒代胱氨酸(selenocystine,Se C)增强抗肿瘤药物顺铂(cisplatin,Cis)对子宫颈癌He La细胞的生长抑制作用及其机制。方法体外培养人子宫颈癌He La细胞,MTT法检测Se C联合Cis对He La细胞的生长抑制。倒置光学显微镜观察细胞形貌的改变。流式细胞术和TUNEL-DAPI双染检测细胞凋亡。Caspase荧光底物检测半胱氨酸蛋白酶caspase-3、caspase-8和caspase-9的活性。JC-1探针检测线粒体膜电位。Western blot检测caspase-3、caspase-9和Bcl-2家族蛋白的表达。结果 Se C(5μmol/L)预处理He La细胞24小时,再联合Cis(5和10μmol/L)共处理24小时,可显著增强Cis对He La细胞的生长抑制,细胞形貌表现为凋亡性改变。机制研究表明,Se C联合Cis对He La细胞的生长抑制主要是通过诱导线粒体介导的凋亡来实现的,表现为Sub-G1峰的升高,caspase-3、caspase-8和caspase-9的激活,TUNEL阳性细胞的增多,线粒体膜电位的耗散和Bcl-2家族蛋白表达的失衡。结论 Se C可协同增敏Cis诱导He La细胞凋亡,为子宫颈癌的治疗提供新策略。Objective To investigate the effect of selenocystine （SeC） on cisplatin （Cis）-induced apoptosis of human cervical cancer HeLa cells. Methods Cultured HeLa cells were pretreated with 5 μmol/L SeC for 24 h, then treated with Cis （5 μmol/L, 10 μmol/L） for another 24h. Cell viability was determined with MTT assay; cell morphology was observed with inverted optical microscope. Caspase substrates were employed to measure the activities of caspase-3, -8 and -9 ; JC-1 probe was used to examine the mitochondrial membrane potential. Expression of Bel-2 family and easpase-3/ 9 were detected with Western blot. Results The growth inhibition of HeLa cells by Cis and Cis-induced apoptosis were enhanced after pretreatment with SeC. Cell apoptosis was confirmed by morphological changes, increased TUNEL-positive cells and Sub-G1 peak. The increase of caspase activation, depletion of mitochondrial membrane potential and unbalance of Bcl-2 family expression were also observed. Conclusion SeC can sensitize Cis-induced apoptosis in HeLa cells, which might be a new strategy for treating human cervical cancer.

关 键 词：宫颈肿瘤/病理学 宫颈肿瘤/药物疗法 HeLa细胞/药物作用 硒代胱氨酸/药理学 顺铂/药理学 抗肿瘤药/药理学 药物协同作用 细胞凋亡/药物作用 线粒体 细胞系 肿瘤 

分 类 号：R737.33[医药卫生—肿瘤] R730.23[医药卫生—临床医学]