首页|期刊导航|中华医学杂志(英文版)|Long-term stable expression of antisense cDNA of cyclin B1 profoundly inhibits the proliferation of tumor cells and suppresses tumorigenicity in implanted mice
Long-term stable expression of antisense cDNA of cyclin B1 profoundly inhibits the proliferation of tumor cells and suppresses tumorigenicity in implanted mice
ZHANG Tao SU Xiao-mei ZHANG Ling LI Ji-cheng WEI Dong WEI Yu-quan ZHANG Ru CHENG Peng CHEN Xian-cheng LIU Huan-yi
中华医学杂志(英文版)2008,Vol.121Issue(15):1433-1438,6.
中华医学杂志(英文版)2008,Vol.121Issue(15):1433-1438,6.
Long-term stable expression of antisense cDNA of cyclin B1 profoundly inhibits the proliferation of tumor cells and suppresses tumorigenicity in implanted mice
Long-term stable expression of antisense cDNA of cyclin B1 profoundly inhibits the proliferation of tumor cells and suppresses tumorigenicity in implanted mice
摘要
Abstract
Background Cyclin B1 (CLB1) is necessary for mitotic initiation in mammalian cells and plays important roles in cancer development. Therefore, a potential strategy in cancer therapy is to suppress the activity of CLB1 by delivering antisense constructs of CLB1 into tumor cells. In previous CLB1 studies, antisense constructs with a short half life were often used and these constructs might not persistently inhibit CLB1.Methods We successfully created a recombinant plasmid encoding the full-length antisense cDNA of mouse cyclin B1 (AS-mCLB1) and transfected this construct to the murine Lewis lung carcinoma (LL/2) and CT-26 colon carcinoma (CT-26) cells. We isolated clones of LL/2 and CT-26 transfectants with stable expression of AS-mGLB1. Reverse transcriptional polymerase chain reaction (RT-PCR) and Western blot were applied to detect the expression of the mRNA and protein levels of CLB1. To further test the efficacy of this strategy in vivo, AS-mCLBl-expressing LL/2 and CT-26 transfectants were implanted into mice.Results We found the expression of the mRNA and protein levels of CLB1 decrease in these trensfectants. The inhibition of CLB1 caused prominent G1 arrest, abnormal morphology, retarded cell growth and an increase in apoptosis. In AS-mCLB1-expressing LL/2 and CT-26 transfectants implanted mice, tumorigenicity was effectively suppressed compared with the controls. In addition, the expression of AS-mCLB1 also significantly increases the survival duration of implanted animals.Conclusion AS-mCLB1 is likely to be useful in future cancer therapy, which may be associated with its ability to down-regulate the expression of CLB1 and then induce G1 arrest and apoptosis in tumor cells.关键词
tumorigenicity/cyclin B1/cancer therapy/antisense cDNAKey words
tumorigenicity/cyclin B1/cancer therapy/antisense cDNA分类
医药卫生引用本文复制引用
ZHANG Tao,SU Xiao-mei,ZHANG Ling,LI Ji-cheng,WEI Dong,WEI Yu-quan,ZHANG Ru,CHENG Peng,CHEN Xian-cheng,LIU Huan-yi..Long-term stable expression of antisense cDNA of cyclin B1 profoundly inhibits the proliferation of tumor cells and suppresses tumorigenicity in implanted mice[J].中华医学杂志(英文版),2008,121(15):1433-1438,6.基金项目
This work was supported by the funds from the Natural Science Foundation of Zhejiang Province, China (No. Y207353) and Science Foundation of Zhejiang Province, China for Postdoctors (No. 2006-bsh-34). (No. Y207353)