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

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.