低表达miR-33a诱导胰腺癌细胞对吉西他滨的耐药  

Down regulation of mi R-33a is involved in gemcitabine chemoresistance in human pancreatic cancer

作　　者：梁晨 王瑧 李影奕 

机构地区：[1]复旦大学附属肿瘤医院肿瘤研究所 [2]复旦大学上海医学院肿瘤学系,上海200032

出　　处：《中国癌症杂志》2015年第2期87-94,共8页China Oncology

基　　金：国家自然科学基金面上项目(30973476;81272727;81472223);上海市浦江人才计划(10PJ1402100)

摘　　要：背景与目的:胰腺癌是一种恶性程度很高的肿瘤。由于其对一线化疗药物吉西他滨的耐受,往往导致预后较差。Micro RNA(mi RNA,mi R)是一类非编码小RNA,参与肿瘤的多种生物学功能。mi R-33a作为代谢相关的mi RNA被广泛研究,而与耐药之间关系的报道较少。该研究通过探讨mi R-33a参与胰腺癌吉西他滨耐药及其作用解析,为胰腺癌化疗提供新的理论依据。方法:采用原位杂交方法检测胰腺癌组织中mi R-33a的表达情况;采用实时荧光定量PCR(Real-time PCR)检测各胰腺癌细胞系中mi R-33a的表达情况。利用SW1990和Miapaca-2胰腺癌亲本细胞株,构建吉西他滨耐药细胞株(SW1990res,Miapaca-2res)及mi R-33a稳定表达细胞株(SW1990-mi R-33a,Miapaca-2-mi R-33a、SW1990res-mi R-33a和Miapaca-2res-mi R-33a);采用细胞毒性实验检测mi R-33a的表达对胰腺癌细胞对吉西他滨敏感性的影响。结果:mi R-33a在胰腺癌组织样本中普遍低表达。与HEK293T正常人胚肾细胞相比,其在各胰腺癌细胞系中均呈低表达。mi R-33a过表达可以增加胰腺癌细胞对吉西他滨的药物敏感性,能有效逆转胰腺癌细胞对吉西他滨的耐药。结论:mi R-33a在胰腺癌组织中低表达,导致胰腺癌患者对吉西他滨获得性耐药。增加mi R-33a表达,从而增强了胰腺癌细胞对吉西他滨的药物敏感性,为开发新型胰腺癌分子靶向治疗药物,联合化疗提供新的理论依据。Background and purpose：Pancreatic cancer is one of the most deadly human malignant neoplasms. Resistance to chemotherapeutic drugs is a major reason responsible for poor prognosis in the treatment of pancreatic cancer patients. MicroRNA （miRNA, miR） is a family of small non-coding RNA molecules, dysregulated miRNA is associated with various tumor biological function. miR-33a has been widely reported as a metabolism-related miRNA, while its relationship with drug resistance has little understand. This study was focused on the effect of miR-33a on gemcitabine chemoresistance in pancreatic cancer to bring the novel theoretical basis to chemotherapy for pancreatic cancer.Methods：In situ hybridization and Real-time PCR were used to analyze the miR-33a expressions in pancreatic cancer tissue sample and cell lines, respectively. Cell counting kit 8 （CCK-8） assay was used to calculate the IC50 value of different pancreatic cancer cells.Results：miR-33a was down-regulated in pancreatic cancer tissue and cell lines compared with para-cancerous tissues and normal HEK293T cells. Moreover, miR-33a over expression not only could enhance the chemosensitivity to gemcitabine in pancreatic cancer cells, but also rescue the gemcitabine resistance in pancreatic cancer cells.Conclusion：Down regulation of miR-33a in pancreatic cancer decreases the chemosensitivity to gemcitabine, resulting in development of acquired gemcitabine chemoresistance. It provides the theoretical basis to develop a new molecular targeted drug to combine with chemotherapy for pancreatic cancer.

关 键 词：miR-33a 胰腺癌 吉西他滨耐药 

分 类 号：R735.9[医药卫生—肿瘤]