【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。更多还原

【Abstract】 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. Micro RNA(mi RNA, mi R) is a family of small non-coding RNA molecules, dysregulated mi RNA is associated with various tumor biological function. mi R-33 a has been widely reported as a metabolismrelated mi RNA, while its relationship with drug resistance has little understand. This study was focused on the effect of mi R-33 a 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 mi R-33 a 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: mi R-33 a was down-regulated in pancreatic cancer tissue and cell lines compared with para-cancerous tissues and normal HEK293 T cells. Moreover, mi R-33 a 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 mi R-33 a 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.更多还原