iNOS抑制剂1400W通过p53途径增强顺铂对宫颈癌SiHa细胞的化疗效果  

iNOS Inhibitor 1400W Enhanced Chemotherapeutic Effect of Cisplatin by p53 Signal in SiHa Cervical Cancer Cells

作　　者：叶君[1] 成雁 陈亚萍[1] 

机构地区：[1]复旦大学附属上海市第五人民医院妇产科,上海200240 [2]江苏省太仓市人民医院妇产科,太仓215400

出　　处：《中国细胞生物学学报》2015年第4期522-528,共7页Chinese Journal of Cell Biology

基　　金：上海市闵行区自然科学基金(批准号:2011MHZ44)~~

摘　　要：该文探讨了iNOS抑制剂1400W联合顺铂对宫颈癌SiHa细胞株生长抑制作用及其机制。应用MTT法检测1400W及顺铂对宫颈癌Si Ha细胞生长的抑制作用;流式细胞仪检测1400W及顺铂对宫颈癌Si Ha细胞凋亡的影响;quantitative RT-PCR和Western blot检测1400W及顺铂对宫颈癌Si Ha细胞p53、鼠双微基因2(murine double minut 2,MDM2)、DNA依赖蛋白激酶(DNA-dependent protein kinase,DNA-PK)蛋白及m RNA表达的影响。结果显示,通过i NOS抑制剂1400W联合顺铂作用于宫颈癌Si Ha细胞株发现,1400W联合顺铂能明显抑制Si Ha细胞生长,其抑制作用与剂量呈正相关。1400W可以增强顺铂诱导的细胞凋亡作用。进一步研究证实,1400W可以抑制顺铂诱导的p53积聚,增加鼠双微基因2及DNA依赖蛋白激酶的表达。该实验结果为治疗宫颈癌患者提供了新的治疗策略,即通过联合使用i NOS抑制剂,可以增强顺铂对宫颈癌细胞的杀伤作用,提高顺铂对宫颈癌患者的治疗作用。The aim of this paper was to explore the effects of iNOS inhibitor 1400 W combined with cisplatin to cervical cancer cell 1ine SiHa and the mechanisms. The effects of 1400 W and cisplatin on Si Ha cell growth were investigated by MTT. The Si Ha cell apoptosis rate was detected by flow cytometry. The expressions of p53, MDM2（murine double minut 2） and DNA-PK（DNA-dependent protein kinase） m RNA and protein in Si Ha cell were detected by quantitative RT-PCR and Western blot. The results showed that 1400 W combined with cisplatin could obviously inhibit Si Ha cell growth, and showed a dose-dependent inhibitory effect on Si Ha cell proliferation. 1400 W enhanced the effect of DDP-induced cell apoptosis. Further study revealed that 1400 W could inhibit DDP-induced overaccumulation of p53 and increased the expression of MDM2 and DNA-dependent protein kinase（DNA-PK）. All of our data suggested that the combinational usage of i NOS inhibitor and DDP was an new strategy in cervical cancer treatment, which could improve the therapeutic effect of DDP on cervical cancer.

关 键 词：顺铂 1400W P53 INOS 宫颈癌SiHa细胞株 

分 类 号：R737.33[医药卫生—肿瘤]