蛋白激酶C-δ阻断剂Rottlerin对人结肠癌细胞的影响及其机理  

The effect of PKC-S inhibitor Rottlerin on human colon cancer cell line SW1116 and its mechanism

作　　者：陈朝飞[1] 房静远[1] 翁玉蓉[1] 孙丹凤[1] 王霞[1] 陆嵘[1] 

机构地区：[1]上海交通大学医学院附属仁济医院上海市消化疾病研究所,200001

出　　处：《中华肿瘤杂志》2006年第8期564-567,共4页Chinese Journal of Oncology

基　　金：国家重点基础研究发展计划(973计划)资助项目(2005CB522408);上海市重点学科建设资助项目(Y0205)

摘　　要：目的研究蛋白激酶C-δ(PKC-δ)阻断剂Rottlerin对人结肠癌细胞的影响及其机理。方法培养人结肠癌细胞SW1116,以Rottlerin 10μmol／L干预24 h,并以DMSO为对照。以定量RT- PCR检测DNA甲基转移酶(DNA methyltransferase,Dnmt)1、3a、3b和抑癌基因APC、p21WAF1和p16INK4A基因转录水平;流式细胞仪分析细胞周期;光学显微镜下观察细胞形态学变化。结果PKC-δ阻断剂Rottlerin可抑制Dnmt1和Dnmt3a表达,上调APC、p21WAF1和p16INK4A转录;Rottlerin明显增加G0／G1期细胞百分比(P=0．02),显著降低G2／M期细胞百分比(P=0．01);Rottlerin可使细胞胞浆增加,体积增大,细胞变得肿胀,轮廓模糊,细胞核分裂相明显减少。结论PKC-δ阻断剂Rottlerin通过调控DNA甲基化水平以及阻断MAPK途径,抑制结肠癌SW1116细胞分裂、增殖。Objective To evaluate the effect of PKC-δ inhibitor Rottlerin on human colon cancer cells and its mechanism. Methods Human colon cancer cell line SW1116 cells were treated with Rottlerin. The transcriptional level of DNA methyltransferase （Dnmt）1, Dnmt3a and Dnmt3b was detected by real-time RT-PCR. Cell cycle distribution was evaluated by flow cytometry （FCM）. In addition, cellular morphological changes were examined by light microscopy. Results PKC-δ inhibitor decreased the expression of Dnmtl, Dnmt3a mRNA, up-regulated APC, p21^WAF1 and p16^INK4A mRNA. Demonstarted by flow cytometry, Rottlerin increased the percentage of cell cycle G0/G1 phase cell numbers （ P = 0.02 ） and decreased the percentage of cell cycle GJM phase cell numbers （P = 0.01 ）. Remarkable changes of cellular morphology were observed under light microscope： The volume and cytoplasm of cells treated with Rottlerin were increased. The cell contour was not very clear, and mitotic figures were less frequently seen. Conclusion PKC-δ inhibitor Rottlerin inhibites cell division and proliferation of the colon cancer SW1116 cells through regulating DNA methylation and blocking the signaling pathway of mitogen-activated protein kinase （ MAPK）.

关 键 词：蛋白激酶C-δ阻断剂 ROTTLERIN 人结肠癌细胞 

分 类 号：R735.3[医药卫生—肿瘤]