大黄素通过下调XIAP的表达增强吉西他滨对胰腺癌的抑瘤作用  

Emodin Enhances Anti-Tumor Effect of Gemcitabine by Down-Regulation Expression of XIAP in Pancreatic Cancer

作　　者：王兆洪[1] 徐锦波[1] 陈敏远 童洪飞[1] 叶兵[1] 林胜璋[1,2] 

机构地区：[1]温州医科大学附属第二医院外科,浙江温州325000 [2]浙江大学附属第一医院肝胆外科,杭州310006

出　　处：《中国药学杂志》2014年第23期2083-2087,共5页Chinese Pharmaceutical Journal

基　　金：浙江省温州市科技计划项目(Y20110123);浙江省自然科学基金资助项目(Y2080708)

摘　　要：目的探讨X-染色体连接的凋亡抑制蛋白(X-linked inhibitor of apoptosis protein,XIAP)在大黄素联合吉西他滨抑制胰腺癌生长中的作用机制。方法将胰腺癌细胞株SW1990分别经空白对照、吉西他滨(20μmol·L-1)、大黄素(40μmol·L-1)以及大黄素(40μmol·L-1)联合吉西他滨(20μmol·L-1)作用24 h后,采用Cell Counting Kit-8(CCK-8)法检测细胞增殖;流式细胞术检测细胞凋亡;蛋白印迹检测细胞中X-染色体连接的凋亡抑制蛋白表达的变化。建立胰腺癌细胞株SW1990的裸鼠皮下移植瘤模型,随机分为对照组(control)、吉西他滨组(gemcitabine)、大黄素组(emodin)以及大黄素联合吉西他滨组,共4组,每组10只,均采用腹腔注射给药,每周3次持续2周,观察药物对皮下移植瘤生长的影响;蛋白印迹检测肿瘤组织中X-染色体连接的凋亡抑制蛋白表达的变化,免疫组织化学染色观察肿瘤组织中Ki-67、X-染色体连接的凋亡抑制蛋白表达的变化。结果与其他各组相比,大黄素联合吉西他滨组细胞存活率明显降低(P<0.05),早期凋亡率显著升高(P<0.05);联合组明显下调胰腺癌细胞中X-染色体连接的凋亡抑制蛋白表达水平。大黄素联合吉西他滨显著抑制裸鼠胰腺癌皮下移植瘤生长,与其他各组相比较均有明显差异(P<0.05);联合组明显下调胰腺癌组织中X-染色体连接的凋亡抑制蛋白表达水平(P<0.05)。结论大黄素可增强吉西他滨对胰腺癌生长的抑制作用,该作用可能部分通过下调X-染色体连接的凋亡抑制蛋白表达和诱导胰腺癌细胞的凋亡而实现。OBJECTIVE To investigate the role of X-linked inhibitor of apoptosis protein（XIAP） playing in anti-tumor effect of emodin in combination with gemcitabine on pancreatic Cancer in vitro and in vivo. METHODS SW1990 cells were treated with gemcitabine, emodin alone or their combination for 24 h, with the untreated cells used as the control. The cellular proliferation was detected by cell counting kit-8 （ CCK-8 ） assay. Degree of cellular apoptosis was assessed by flow cytometry. Western blotting was used to detect the protein expression of XIAP in SW1990 cells. SW1990 cells were injected subcutaneously into nude mice to establish pancreatic xenograft tumors. Tumor beating animals were divided into the following treatment groups： control group, gemcitabine group, emodin group and combination group. Each group consisted of ten nude mice. Gemcitabine and emodin was administered intraperitoneally three times a week. After the mice were treated for 2 weeks, the volume of xenograft tumors were monitored. Western blotting was used to detect the protein expression of NF-κB and XIAP in pancreatic tumor. Immunohistochemistry was used to test the expression of Ki-67,XIAP in the tumors. RESULTS Compared with the other groups, the cell survival rate of the combination group was significantly lowered（ P 〈 0. 05 ）. Emodin combined with gemcitabine induced a higher percentage of apoptosis in pancreatic cancer cells than that of emodin or gemcitabine alone （ P 〈 0. 05 ）. The expression of NF-κB and XIAP in pancreatic carcinoma cells were obviously down-regulated in combination group. The mean volume of xenograft tumor was more significantly reduced in combination group than other groups （ P 〈 0. 05 ）. The expression of XIAP in tumor tissues of combination group were down-regulated more significantly than other groups （ P 〈 0. 05 ）. CONCLUSION Emodin enhances the growth inhibition of pancreatic cancer induced by gemcitabine in vitro and in vivo, which may be realized partly through the down-regulati

关 键 词：大黄素 胰腺肿瘤 吉西他滨 X-染色体连接的凋亡抑制蛋白 

分 类 号：R965[医药卫生—药理学]