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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 investigate the effect of STAT3 signal transduction pathway on the growth and apoptosis of human cervical carcinoma xenografts in nude mice and its relationship with Survivin expression. Methods: The cervical cancer xenografts in nude mice were established and treated with AG490 alone or in combination with cisplatin (DDP). The growth of nude mice xenografts was observed and recorded during the treatment. The tumor volume, Growth inhibition rate, tumor growth curve were plotted to observe the weight changes of nude mice after treatment. Immunohistochemistry and Western blot were used to detect the expression of P-STAT3 and Survivin, and the apoptosis was detected by flow cytometry. Results: AG490 and DDP could inhibit the growth of cervical cancer xenografts and promote the apoptosis of cervical cancer cells. At the same time, the expression and activity of P-STAT3 and Survivin in cervical cancer cells were significantly decreased. The combination of AG490 and DDP could act synergistically and AG490 could enhance DDP drug sensitivity and reduce drug side effects. Conclusion: JAK kinase inhibitor AG490 combined with DDP may provide a new theoretical basis for the treatment of cervical cancer.