DNMT3a对胰腺癌细胞吉西他滨敏感性的影响  

Effect of DNMT3a on the Chemosensitivity of Pancreatic Cancer Cells to Gemcitabine

作　　者：荆薇[1] 宋娜[2,3] 车晓芳[2,3] 侯科佐[2,3] 杨向红[4] JING Wei;SONG Na;CHE Xiaofang;HOU Kezuo;YANG Xianghong(The First Department of Oncology,Shengjing Hospital,China Medical University,Shenyang 110022,China;Department of Medical Oncology, The First Hospital,China Medical University,Shenyang 110001,China;Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province,The First Hospital,China Medical University,Shenyang 110001,China;Department of Pathology,Shengjing Hospital,China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院第一肿瘤科,沈阳110022 [2]中国医科大学附属第一医院肿瘤内科,沈阳110001 [3]中国医科大学附属第一医院辽宁省肿瘤药物及生物治疗重点实验室,沈阳110001 [4]中国医科大学附属盛京医院病理科,沈阳110004

出　　处：《中国医科大学学报》2018年第10期900-904,共5页Journal of China Medical University

基　　金：辽宁省高等学校基本科研项目青年项目(LQNK201711)

摘　　要：目的研究DNA甲基转移酶3a (DNMT3a)对胰腺癌Panc-1细胞吉西他滨敏感性的影响,并探讨其作用机制。方法 MTT法检测吉西他滨对人胰腺癌细胞增殖的影响;应用siRNA下调DNMT3a表达;Western blotting确认DNMT3a蛋白敲除效率,检测吉西他滨及siRNA DNMT3a对p-STAT3、 STAT3和胞苷脱氨酶(CDA)表达的影响。流式细胞仪检测细胞凋亡。结果下调DNMT3a表达能够增加胰腺癌Panc-1细胞对吉西他滨的敏感性。下调DNMT3a表达能够降低由吉西他滨引起的p-STAT3和CDA表达上调。下调DNMT3a表达能够增加由吉西他滨诱导的细胞凋亡。结论下调DNMT3a可以通过抑制CDA及STAT3通路促进胰腺癌细胞吉西他滨的敏感性。Objective To evaluate the effect and mechanism of DNA methyltransferase-3a(DNMT3a)on the chemosensitivity of pancreatic cancer cells to gemcitabine(GEM).Methods MTT assay was used to determine the effect of GEM and DNMT3a on the proliferation of pancreatic cancer cell line,Panc-1.Cells were transfected with siRNA to downregulate the expression of DNMT3a.The expression of DNMT3a,CDA,p-STAT3s,and STAT3 in PANC-1 cells transfected with siDNMT3a were detected by Western blotting.Flow cytometry was used to detect apoptosis.Results Downregulation of DNMT3a expression increased the sensitivity of Panc-1 cells to GEM,reduced the upregulation of p-STAT3 and CDA expression induced by GEM,and increased the apoptosis induced by GEM.Conclusion Downregulation of DNMT3a expression increased the chemosensitivity of pancreatic cancer cells to GEM by inhibiting the activation of STAT3 and expression of CDA.

关 键 词：药物敏感性 吉西他滨 胰腺癌 DNA甲基转移酶3a 

分 类 号：R735.9[医药卫生—肿瘤]