论文部分内容阅读
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 effect of JAK / STAT pathway inhibitor AG490 combined with cisplatin (DDP) on the growth of cervical cancer xenografts in nude mice and to investigate the effect of AG490 on the growth of human cervical carcinoma xenografts in nude mice by blocking STAT3 pathway Inhibition and its relationship with caspase-3 protein expression. Methods: Nude mice xenograft model of human cervical carcinoma (HeLa) cells was established and divided into groups. AG490 alone or in combination with DDP nude mice. During the measurement of nude mice body weight and tumor volume, tumor weight was measured to calculate the inhibition rate. Flow cytometry was used to detect the apoptosis in tumor tissue. The expression of P-STAT3 and caspase-3 protein in tumor tissue was detected by immunohistochemistry. Data are processed using SPSS10.0 statistical software. Results: On the 7th day after treatment, the tumor volume in the combination group (265.51 ± 23.74) and the AG490 group (382.89 ± 16.54) was significantly reduced compared with the combination group (250.66 ± 18.55) (P <0.05 and P <0.001). There was significant difference between DDP group and control group (P <0.05). The tumor inhibition rates of the control group, the DDP group, the AG490 group and the combination group were 0, 51.2%, 33.6% and 59.2%, respectively. The antitumor effect of the combination group was more obvious than that of the single group (P <0.05, P <0.001) . FCM analysis showed that apoptotic peaks were found in the tumor samples of the experimental group, with apoptotic rates of (52.1 ± 1.3)%, (39.5 ± 0.4)% and (66.7 ± 1.8)%, respectively, % Of the difference was statistically significant (P <0.05). The range of tumor necrosis was obviously related to the treatment. The range of tumor necrosis in combination therapy group was the largest, with statistical significance (P <0.05). The results of immunohistochemistry showed that P-STAT3 was down-regulated and caspase-3 was up-regulated in combination group, but there was no negative correlation between them (r = -0.074, P> 0.05). Conclusion: AG490 can inhibit the growth of cervical cancer and increase the expression of P-STAT3, but has no direct effect on the expression of caspase-3. AG490 and DDP combined application can further improve the treatment effect.