摘要:目的:探讨Janus激酶(JAK)特畀性抑制剂AG490联合化疗药物健择对人胰腺癌细胞系SW1990的生长增殖及STAT3转导通路的影响和其机制、方法:人胰腺癌细胞系SWl990分为对照组、AG490组、健择组及AG490+健择处理组.培养48h后,MTT法检测细胞增殖状态,流式细胞仪检测细胞凋亡.Western blot和RT-PCR检测STAT3,Cyclin D1,Bcl—xL,Bax,Survivin的表达情况.结果:AG490组和健择组的细胞增殖明显低于对照组(2.20±0.25,2.30±0.220vs3.78±0.42,P〈0.05),凋亡率明显高于对照组(35.40%±3.08%.34.64%±1.38%vs16.49%±1.45%,P〈0.05).并且,AG490+健择组细胞增殖(1.49±0.15)明显低于明显低于AG490或健择组(P〈0.05),而凋亡率(43.80%±1.57%)则明显高于AG490或健择组(P〈0.05).AG490处理SW199048h后,P—STAT3表达明显低于对照组(13.83%±0.64%vs 79.87%±1.43%,P〈0.05)。同时Cyclin D1(mRNA:15、63%±0.59%vs43.83%±0.64%.P〈0.05:蛋白:17.50%±0.92%vs49.87%±1.27%.P〈0.05).Bcl-xL(mRNA:13.93%±0.21%vs75.70%±0.46%.P〈0.05:蛋白:34.17%±1.70%vs83.93%±0.80%,P〈0.05)和Survivin(mRNA:58-27%±0.42%vs82.93%±1.68%,P〈0.05;蛋白:13.23%±1.03%vs18.60±1.08%.P〈0.05)表达也明显降低,而Bax的表达则明显增高fmRNA:10-33%±1.18%vs5.43%±0.70%,P〈0.05;蛋白:13.07%±1.04%vs6.23%±2.40%,P〈0.05),健择处理组上述指标与对照组相似.
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