低表达miR-33a诱导胰腺癌细胞对吉西他滨的耐药

doi:10.3969/j.issn.1007-3969.2015.02.002

中国癌症杂志 ›› 2015, Vol. 25 ›› Issue (2): 87-94.doi: 10.3969/j.issn.1007-3969.2015.02.002

低表达miR-33a诱导胰腺癌细胞对吉西他滨的耐药

梁晨，王瑧，李影奕

复旦大学附属肿瘤医院肿瘤研究所，复旦大学上海医学院肿瘤学系，上海 200032

出版日期:2015-02-28 发布日期:2015-05-13
通信作者: 李影奕　E-mail:liyingyi@fudan.edu.cn
基金资助:
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)。

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

LIANG Chen, WANG Zhen, LI Yingyi

Cancer Research Institute, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Published:2015-02-28 Online:2015-05-13
Contact: LI Yingyi E-mail: liyingyi@fudan.edu.cn

摘要/Abstract

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。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(SW1990^res，Miapaca-2^res)及miR-33a稳定表达细胞株(SW1990-miR-33a，Miapaca-2-miR-33a、SW1990^res-miR-33a和Miapaca-2^res-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。

关键词: , miR-33a, 胰腺癌, 吉西他滨耐药

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. 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 metabolismrelated 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.

Key words: miR-33a, Pancreatic cancer, Gemcitabine chemoresistance

梁晨,王瑧,李影奕. 低表达miR-33a诱导胰腺癌细胞对吉西他滨的耐药[J]. 中国癌症杂志, 2015, 25(2): 87-94.

LIANG Chen, WANG Zhen, LI Yingyi. Down regulation of miR-33a is involved in gemcitabine chemoresistance in human pancreatic cancer[J]. China Oncology, 2015, 25(2): 87-94.

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低表达miR-33a诱导胰腺癌细胞对吉西他滨的耐药

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

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