中国癌症杂志
中國癌癥雜誌
중국암증잡지
CHINA ONCOLOGY
2015年
2期
87-94
,共8页
miR-33a%胰腺癌%吉西他滨耐药
miR-33a%胰腺癌%吉西他濱耐藥
miR-33a%이선암%길서타빈내약
miR-33a%Pancreatic cancer%Gemcitabine chemoresistance
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。MicroRNA(miRNA，miR)是一类非编码小RNA，参与肿瘤的多种生物学功能。miR-33a作为代谢相关的miRNA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miR-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miR-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miR-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miR-33a稳定表达细胞株(SW1990-miR-33a，Miapaca-2-miR-33a、SW1990res-miR-33a和Miapaca-2res-miR-33a)；采用细胞毒性实验检测miR-33a的表达对胰腺癌细胞对吉西他滨敏感性的影响。结果：miR-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。miR-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：miR-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miR-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。
揹景與目的：胰腺癌是一種噁性程度很高的腫瘤。由于其對一線化療藥物吉西他濱的耐受，往往導緻預後較差。MicroRNA(miRNA，miR)是一類非編碼小RNA，參與腫瘤的多種生物學功能。miR-33a作為代謝相關的miRNA被廣汎研究，而與耐藥之間關繫的報道較少。該研究通過探討miR-33a參與胰腺癌吉西他濱耐藥及其作用解析，為胰腺癌化療提供新的理論依據。方法：採用原位雜交方法檢測胰腺癌組織中miR-33a的錶達情況；採用實時熒光定量PCR(Real-time PCR)檢測各胰腺癌細胞繫中miR-33a的錶達情況。利用SW1990和Miapaca-2胰腺癌親本細胞株，構建吉西他濱耐藥細胞株(SW1990res，Miapaca-2res)及miR-33a穩定錶達細胞株(SW1990-miR-33a，Miapaca-2-miR-33a、SW1990res-miR-33a和Miapaca-2res-miR-33a)；採用細胞毒性實驗檢測miR-33a的錶達對胰腺癌細胞對吉西他濱敏感性的影響。結果：miR-33a在胰腺癌組織樣本中普遍低錶達。與HEK293T正常人胚腎細胞相比，其在各胰腺癌細胞繫中均呈低錶達。miR-33a過錶達可以增加胰腺癌細胞對吉西他濱的藥物敏感性，能有效逆轉胰腺癌細胞對吉西他濱的耐藥。結論：miR-33a在胰腺癌組織中低錶達，導緻胰腺癌患者對吉西他濱穫得性耐藥。增加miR-33a錶達，從而增彊瞭胰腺癌細胞對吉西他濱的藥物敏感性，為開髮新型胰腺癌分子靶嚮治療藥物，聯閤化療提供新的理論依據。
배경여목적：이선암시일충악성정도흔고적종류。유우기대일선화료약물길서타빈적내수，왕왕도치예후교차。MicroRNA(miRNA，miR)시일류비편마소RNA，삼여종류적다충생물학공능。miR-33a작위대사상관적miRNA피엄범연구，이여내약지간관계적보도교소。해연구통과탐토miR-33a삼여이선암길서타빈내약급기작용해석，위이선암화료제공신적이론의거。방법：채용원위잡교방법검측이선암조직중miR-33a적표체정황；채용실시형광정량PCR(Real-time PCR)검측각이선암세포계중miR-33a적표체정황。이용SW1990화Miapaca-2이선암친본세포주，구건길서타빈내약세포주(SW1990res，Miapaca-2res)급miR-33a은정표체세포주(SW1990-miR-33a，Miapaca-2-miR-33a、SW1990res-miR-33a화Miapaca-2res-miR-33a)；채용세포독성실험검측miR-33a적표체대이선암세포대길서타빈민감성적영향。결과：miR-33a재이선암조직양본중보편저표체。여HEK293T정상인배신세포상비，기재각이선암세포계중균정저표체。miR-33a과표체가이증가이선암세포대길서타빈적약물민감성，능유효역전이선암세포대길서타빈적내약。결론：miR-33a재이선암조직중저표체，도치이선암환자대길서타빈획득성내약。증가miR-33a표체，종이증강료이선암세포대길서타빈적약물민감성，위개발신형이선암분자파향치료약물，연합화료제공신적이론의거。
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.
