大黄素可通过下调NF-κB的表达逆转胰腺癌吉西他滨耐药细胞株的耐药作用  

作　　者：张言涛[1] 成伯宁 刘殿雷[1] 黄海[1] 沈肖曹[3] 

机构地区：[1]杭州市中医院外一科,310007 [2]杭州市西溪医院普内科,310023 [3]浙江大学医学院附属第二医院,310009

出　　处：《浙江临床医学》2017年第12期2230-2232,共3页Zhejiang Clinical Medical Journal

基　　金：浙江省医药卫生科技项目（2018274756）;浙江省中医药管理局优秀青年基金项目（2013ZQ026）;杭州市科技发展计划项目（20140733Q34）

摘　　要：目的探讨大黄素逆转胰腺癌耐药细胞株Bxpc-3／Gem耐药作用及其逆转机制。方法采用浓度递增法诱导建立耐药细胞株Bxpc-3／Gem；胰腺癌细胞株Bxpc-3／Gem和Bxpc-3经不同浓度大黄素作用48h，MTT法检测细胞增殖；以及大黄素（40μm）及吉西他滨（20μm）处理细胞48h，应用MTT法检测BXpc-3／Gem和Bxpe-3细胞增殖；RT-Pc褂釜测经大黄隶及吉西他滨处理后的Bxpc-3／Gem细胞中NF-κB基因的表达水平；凝胶电泳迁移率实验（EMSA）检测经大黄素及吉西他滨处理后Bxpc-3／Gem细胞中NF-κB的活性。结果大黄素对Bxpc-3／Gem细胞的增殖抑制作用呈明显的浓度依赖性；大黄素显著增强吉西他滨对Bxpc-3／Gem细胞的增殖抑制作用；大黄素单独及联合吉西他滨均可下调细胞中NF-κB基因的表达，抑制NF-κB的活性。结论大黄素可以逆转胰腺癌耐药细胞株Bxpc-3／Gem的耐药作用，其机制可能是下调NF-κB的表达，抑制其活性从而增强胰腺癌细胞对吉西他滨的敏感性。Objective To investigate the reversal effect and mechanism of emodin on gemcitabine resistant of pancreatic cancer cell line （ Bxpc-3/ Gem ） . Methods A gemcitabine-resistant cell line Bxpc-3/Gem was derived from the human pancreatic cancer cell line Bxpc-3.The pancreatic cancer cell lines Bxpc-3/Gem and Bxpc-3 were treated with various concentrations of emodin, gemcitabine and the combination of emodin ＋ gemcitabine, Bxpc-3/Gem cells were treated with emodin （ 40 μ m ） and gemcitabine （ 20 μm ） alone or together for 48 h, and then the changes in gene expression were detected by RT-PCR, DNA-binding activity of NF- κ B by EMSA. Results Emodin reduced Bxpc-3/Gem cell proliferation and caused apoptosis in a dose-dependent manner. Emodin and gemcitabine combination treatments resulted in decreased cell proliferation. In addition, combination treatments resulted in downregulation of gene expression of NF-κB, as well as inhibition of NF- κB function. Conclusion These observations suggest that emodin can sensitize the pancreatic cancer gemcitabine-resistant cell line Bxpc-3/Gem to gemcitabine therapy via NF- κ B.

关 键 词：大黄素 胰腺癌 耐药 NF-ΚB 

分 类 号：R737.31[医药卫生—肿瘤]