Lin28A促进结肠癌细胞对5-FU化疗敏感性的实验研究

Experimental Study on Effect of Lin28A on the Sensitivity of Colon Cancer 5-FU Chemotherapy

目的:探讨Lin28A对结肠癌5-氟尿嘧啶(5-FU)化疗敏感性的影响及其分子机制。方法:免疫组化方法检测人结肠癌和正常粘膜组织中Lin28A蛋白表达情况;荧光素酶法检测HCT116细胞活性;实时荧光定量PCR方法检测HCT116细胞中Let-7表达水平。结果:73.3%人结肠癌患者Lin28A蛋白表达上调;过表达Lin28A组与对照组相比,5-FU处理后细胞活性显著降低(P_(60μg)<0.01,P_(80μg)<0.01),Let-7表达显著降低;过表达Let-7组与对照组相比,5-FU治疗后细胞活性显著降低(P_(40μg)<0.05,P_(60μg)<0.01,P_(80μg)<0.01)。结论:Lin28A可增强肿瘤细胞化疗敏感性,而且这一效应不依赖Let-7。

Objective： To investigate the effect of Lin28 A on the sensitivity of colon cancer 5-FU chemotherapy and its molecular mechanism. Methods： The expression of Lin28 A in human colon carcinoma and normal mucosa was detected by immunohistochemistry method. HCT116 cell activity was detected by luciferase assay. The Let-7 expression in HCT116 cells was detected by real-time quantitative PCR method. Results： Lin28 A is up-regulated in 73.3 % of colon cancer patients. After 5-FU treatment, the cell activity was significantly decreased（P60μg〈0.01,P80μg〈0.01） in Lin28 A over-expressing cells compared to control cells. The Let-7 expression was significantly decreased at the same time. Compared with the control group, the cell activity after 5-FU treatment in Let-7 overexpression group was significantly lower than that in the control group（P40μg〈0.05, P60μg〈0.01, P80μg〈0.01）. Conclusions： The effect of Lin28 A increasing chemosensitivity of cancer cells is in a Let-7 independent manner.