一磷酸腺苷活化蛋白激酶对环氧合酶-2表达与5氟-尿嘧啶治疗结肠癌敏感性的关系

Expression of cyclooxygenase-2 by the activation of adenosine monophosphate protein kinase and the relationship between the expression and chemosensitivity of 5-Fluorour-acil in colon cancer

目的探讨一磷酸腺苷活化蛋白激酶(AMPK)对环氧合酶-2(COX-2)蛋白表达及结肠癌5-氟尿嘧啶(5-Fu)化疗敏感性的影响。方法选用HT-29结肠癌细胞株,按照HT-29细胞的培养液不同,分为空白对照组(常规培养)、5-Fu培养组、5-氨基咪唑-4-甲酰胺核苷酸(AICAR)培养组、5-Fu+AICAR培养组。用western blot法测定各组中P-ACC和COX-2的表达,并分别于培养6、12、24小时分析5-Fu培养组和5-Fu+AICAR培养组中P-ACC和COX-2的表达水平的变化;用MTT法检测12、24、48小时各组细胞的存活率。结果5-Fu组作用后COX-2蛋白上调,AICAR致P-ACC表达后,可下调COX-2蛋白的表达;5-Fu联合AICAR可降低细胞存活率。结论AMPK的激活可能下调COX-2表达,并可能提高以5-Fu治疗为基础的结肠癌化疗敏感性。

Objective To investigate the expression of cyclooxygenase-2 （COX-2） by the activation of adenosine monophosphate protein kinase （AMPK） and the relationship between the expression and chemosensitivity of 5-Fluorouracil in colon cancer. Methods We chose HT-29 colon carcinoma cells as our study object and divided them into 4 groups according to the culture media ： blank control （ conventional culture） , 5-Fu, AICAR, 5-Fu ＋ AICAR groups. Western blot were performed to detect the expression of P-ACC and COX-2 in each group, and the expression of P-ACC and COX-2 at 6, 12, 24 hours after culture in 5-Fu and 5-Fu ＋ AICAR groups. Cell viability was measured by MTT. Results Compared with control group, we found upregulation of COX-2 in 5-Fu group and down-regulation of COX-2 when P-ACC had been expressed induced by AICAR in 5-Fu ＋ AICAR group;Combination of 5-Fu and AICAR minimized cell viability. Conclusion Activation of AMPK can decrease the expression of COX-2, and may increase the chemosensitivity of 5-Fu drug in the treatment of colon cancer.