摘要
目的:观察JAK/STAT通路阻断剂AG490联合顺铂(Cis-diaminedichloro-platinum,DDP)对宫颈癌裸鼠移植瘤生长的影响,探讨AG490通过阻断STAT3通路对人宫颈癌裸鼠移植瘤生长抑制作用及与caspase-3蛋白表达的关系。方法:建立人子宫颈癌(HeLa)细胞裸鼠异种移植瘤模型并分组。AG490单用或联合DDP处理各组裸鼠。用药期间测量裸鼠体重和肿瘤体积,检测瘤重计算抑瘤率。流式细胞术检测肿瘤组织中细胞凋亡情况,免疫组化检测移植瘤组织中P-STAT3和caspase-3蛋白表达。数据均用SPSS10.0统计软件处理。结果:治疗第7天与DDP组(265.51±23.74)和AG490组(382.89±16.54)比,联合用药组(250.66±18.55)肿瘤体积明显缩小(P<0.05和P<0.001)。DDP组裸鼠体重与联合用药组差异有统计学意义(P<0.05)。对照组、DDP组、AG490组和联合用药组抑瘤率分别为0,51.2%,33.6%,59.2%,联合用药组的抑瘤作用比单用组更加明显(P<0.05,P<0.001)。FCM分析表明,实验组的肿瘤标本中均可见凋亡峰,凋亡率分别是(52.1±1.3)%,(39.5±0.4)%和(66.7±1.8)%,与对照组(10.2±2.4)%的差异有统计学意义(P<0.05)。肿瘤坏死范围与用药明显相关,联合用药组肿瘤的坏死范围最大,与单独用药组的差异有统计学意义(P<0.05)。免疫组化结果显示,联合用药组P-STAT3表达下调,caspase-3表达上调,但二者无负相关(r=-0.074,P>0.05)。结论:AG490对宫颈癌生长有一定的抑制作用,增加P-STAT3表达,但对caspase-3表达无直接作用。AG490与DDP联合应用可进一步提高治疗效果。
Objective：To Observe the influence of AG490 combined DDP on the growth of human cervical cancer in nude mice and to explore the relationship between the caspase-3 expression and STAT3 pathway. Methods：After the establishment of the model, mice were divided into 4 groups （eight in each） randomly. The control group and three model groups received DDP, AG490, AG490＋DDP respectively by intraperitoneal injection. The weight of nude mice and tumor size were measured. The tumor weight and inhibition rate were evaluated, when the mice were sacrificed after 2 weeks treatment. Cell apoptosis was detected by flow cytometry （FCM）. The necrotic degree and range were observed by the microscope. Statistical software SPSS10.0 was used to deal with all the data. Results： Compared with the combination group, there were significant differences（P〈0.001 ） in DDP group and AG490 group （P〈0.05 ,P〈0.001 ） in the treatment of the first 7 days. There were significant differences in DDP group and combination group in weight change （ P〈0.05 ）. The apoptosis rates of the three groups were （52.1 ± 1.3 ） %, （ 39.5 ±0.4） %and （66.7±1.8）% respectively,and there were significant differences compared with the control group （10.2±2.4）% （P〈0.05）. There were significant differences between the combination group and AG490 group, DDP group （P〈0.05） on the average rate of tumor necrosis. There were no significant relevance between expressions of P-STAT3 protein and caspase-3 protein in AG490 group （ r = 20. 074, P〉0.05 ）. Conclusion： AG490 suppresses the growth of human cervical cancer in nude mice. Combination of AG490 and DDP may be useful in treatment of human cervical cancer.
出处
《现代妇产科进展》
CSCD
北大核心
2009年第8期578-583,共6页
Progress in Obstetrics and Gynecology
基金
兰州大学医学基金资助(No:LZUYX2007.5)
