RNAi沉默Snail增加结肠癌对5氟尿嘧啶敏感性研究  

Suppression of Snail by Short Interfering RNA Enhanced 5-fluorouracil-induced Cell Death in Colon Cancer Cells

作　　者：周晓刚[1] 王凯[1] 沈小刚[1] 王林[1] 覃先鹏 郭志义[1] ZHOU Xiao-gang WANG Kai SHEN Xiao-gang WANG Lin QIN Xian-peng GUO Zhi-yi(Sichuan Academy of Medical Sciences （Gastrointestinal Surgery of People＇s Hospital in Sichuan Province）, Chengdu, Sichuan, 610072, China)

机构地区：[1]四川省医学科学院(四川省人民医院胃肠外科),四川成都610072

出　　处：《现代生物医学进展》2017年第10期1818-1821,1910,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年科学基金项目(81301910)

摘　　要：目的:研究Snail的抑制是否能增加耐药结肠癌细胞对5-FU的敏感性,评估其可能的信号转导通路。方法:使用5-氟尿嘧啶耐药HCT116细胞(HCT116/5-FU),评估细胞形态及分子的变化。通过靶向人Snail基因小干扰RNA(si RNA)抑制Snail的表达。Annexin V/PI染色用于评估5-FU诱导的细胞凋亡。Western blot检测caspase以及可能的丝裂原活化蛋白激酶(MAPK)和线粒体途径。结果:HCT116细胞对5-Fu耐药性的获得诱导了与EMT一致的形态学变化。RNA干扰沉默Snail逆转HCT116/5-FU细胞EMT并增加了5-FU耐药HCT116细胞对5-FU的敏感性。可能的机制涉及JNK与线粒体途径的激活。结论:EMT样表型的改变与HCT116细胞对5-FU耐药相关;si RNA介导的Snail下调可能是一个潜在的克服5-FU化疗耐药的治疗方法。Objective： We tested whether Snail suppression could increase the sensitivity of 5-FU-resistant colon cancer cells to 5-FU and further assessed possible signaling transduction pathways. Methods： Using a 5-fluorouracil-resistant HCTII6 ceils （HCT116/5-FU）, we assessed the cellular morphology and molecular changes consistent with EMT. Expression of Snail was suppressed using a small interfering RNA （siRNA） targeting human Snail mRNA. Annexin V/propidium iodide （PI） apoptosis assay was performed to assess the 5-FU -induced apoptosis. The Caspase as well as possible MAPKs and mitochondrial pathways were determined by Western blot. Results： Acquisition of 5-FU resistance induces morphologic changes consistent with EMT in HCT116 cells. Silencing of Snail by RNA interference reversed the EMT of HCT116/5-FU cells and increased the sensitivity of 5-FU-resistant HCT116 cells to 5-FU, the possible mechanism involve activation of JNK/mitochondrial pathway. Conclusion： EMT-like phenotypie changes is associated with 5-FU resistance in HCT116 cells, siRNA-mediated Snail knockdown could be a potential novel therapeutic approach to overcoming chemoresistance during 5-FU chemotherapy.

关 键 词：上皮间质转化 结肠癌 5氟尿嘧啶 SNAIL 

分 类 号：R-33[医药卫生] R735.35