AG490单用或联合顺铂对人宫颈癌裸鼠移植瘤STAT3/Survivin信号转导通路的影响

Effects of AG490 alone or AG490 combined with cisplatin on STAT3/Survivin signal transduction pathway in transplanted tumor of nude mice with human cervical cancer

目的:探讨STAT3信号转导通路对人宫颈癌裸鼠移植瘤生长、凋亡的影响以及与Survivin表达之间的关系。方法:建立宫颈癌裸鼠移植瘤模型并分组,AG490单用或联合顺铂(DDP)处理各组裸鼠,治疗期间观察并记录各组裸鼠皮下移植瘤的生长情况,计算肿瘤体积、肿瘤生长抑制率,绘制肿瘤生长曲线,观察用药后裸鼠体重变化;免疫组化、Western blot分别检测移植瘤P-STAT3、Survivin表达,流式细胞技术检测细胞凋亡。结果:AG490与DDP可以抑制宫颈癌移植瘤生长,促进宫颈癌细胞凋亡,同时使宫颈癌细胞P-STAT3、Survivin表达与活性明显下降;联合应用AG490与DDP,可以起协同作用,AG490可以增强DDP的药物敏感性并且减轻药物副作用。结论:JAK激酶抑制剂AG490与DDP联合应用可能为治疗宫颈癌提供了新的理论基础。

Objective： To explore the effect of STAT3 signal transduetion pathway on the growth and apoptosis of transplanted tumor of nude mice with human cervical cancer and its relationship with the expression of Survivin. Methods： The models of transplanted tumor of nude mice with human cervical cancer were established, then the mice were divided into different groups, AG490 alone or AG490 combined with cisplatin were used to treat the nude mice in different groups, the growth situations of subcutaneous transplanted tumor in different groups were observed and recorded during the treatment, the volumes of transplanted tumor and the inhibiting rates of growth of transplanted tumor were calculated, the curves of growth of transplanted tumor in different groups were drawn, the changes of body weight of nude mice after treatment were observed ; immunohistochemistry and Western blot were used to detect the expression levels of P - STAT3 and Survivin in transplanted tumor, respectively; cell apoptosis was detected by flow cytometry. Results： AG490 and cisplatin inhibited the growth of transplanted tumor of cervical cancer, promoted apoptosis of cervical cancer cell, induced the decrease of P - STAT3 and Survivin expressions and activities in cervical cancer cell; AG490 combined with cisplatin played an synergistic effect, ACA90 could enhance the drug sensitivity and relieve the adverse reaction of cisplatin. Conclusion： AG490 combined with cisplatin may provide a new theoretical basis for the treatment of cervical cancer.