诺斯卡品逆转人卵巢癌裸鼠移植瘤对顺铂耐药的作用及机制

The reversal effect and action mechanism of noscapine on the drug resistant of cisplatin in nude mice with transplanted human ovarian cancer

目的探讨微管抑制剂诺斯卡品(NOS)逆转人卵巢癌细胞株SKOV3/DDP裸鼠皮下移植瘤对顺铂(DDP)耐药的作用及其机制。方法建立人卵巢癌裸鼠移植瘤模型,分为对照组、DDP组、NOS组、NOS与DDP联合组,每组6只。观察各组裸鼠饮食和精神状态,测量裸鼠的体重及移植瘤的体积,并绘制肿瘤生长曲线。用网搓法制备单细胞悬液,采用流式细胞术检测移植瘤细胞周期和细胞凋亡率的变化,细胞中X链锁凋亡抑制蛋白(XIAP)、半胱氨酸天冬氨酸蛋白酶(Caspase-3)、B细胞淋巴瘤/白血病-2(Bcl-2)和生存素(Survivin)蛋白表达。结果联合组裸鼠移植瘤体积明显小于对照组和其他用药组(P<0.05)。与对照组和DDP组比较,联合组皮下移植瘤细胞凋亡率显著增加(P<0.05),G2/M期细胞比例增多(P<0.05),细胞中XIAP、Bcl-2和Survivin蛋白表达降低(P<0.05),Caspase-3蛋白表达升高(P<0.05)。结论 NOS增加了移植瘤细胞对DDP的敏感性,逆转其对DDP的多药耐药,其机制可能与XIAP、Bcl-2和Survivin蛋白表达的下调,Caspase-3蛋白表达的上调有关。

Objective To investigate the reversal effect and relative mechanism of noscapine （ NOS ） on the drug resistant of cisplatin （ DDP） in nude mice with transplanted human ovarian cancer cell line SKOV 3/DDP.Methods The animal models with transplanted human ovarian cancer were successfully established in 24 BALB/c nu/nu mice,then the mice were randomly divided into control group ,DDP group,NOS group and combined treatment group （NOS＋DDP）,with 6 mice in each group .The appetite and mental state of the nude mice in different groups were observed .The weight of the nude mice and size of the xenograft tumor were measured and tumor growth curve was drew .The xenograft tumor was made into single cell suspension fluid with nets rub method,and the cell cycle,cell apoptosis rate,the expression levels of XIAP,Caspase-3,Bcl-2 and Survivin proteins in tumor tissues were detected by flow cytometry .Results The xenograft tumor size in combined treatment group was significantly smaller than that in the other three groups （ P ＆lt;0 .05 ） .As compared with those in control group and DDP group , the tumor cell apoptosis rate and cell percentage at G 2/M phase in combined treatment group were significantly increased （ P ＆lt;0.05）,however,the expression levels of XIAP,Bcl-2 and Survivin proteins were obviously decreased,but the expression levels of Caspase-3 protein were significantly increased （ P ＆lt;0.05）.Conclusion NOS can increase the sensitivity and reverse the drug resistance of xenograft tumor cells to DDP , and its action mechanism may be correlated with downregulation of expression levels of XIAP , Bcl-2 and Survivin protein , and with upregulation of expression levels of Caspase-3 protein in xenograft tumor tissues of nude mice .