关键词: 鼻咽肿瘤, CD133+肿瘤干细胞, 肿瘤靶向治疗, 端粒酶

Abstract: Abstract:Objective To explore the mechanism of  targeted inhibition of hTERTp/TK/pGL3 vector on  the telomerase activity and its killing effect on nasopharyngeal cancer stem cells.Methods The nasopharyngeal carcinaoma CD133+ stem cells,CD133－tumor cells, human umbilical vein endothelial cells (ECV cells) (control group) and nasopharyngeal carcinaoma SUNE unsorted cells were transfected by hTERTp/TK/pGL3 vector and its control vectors (CMV/TK/pGL3 and TK/pGL3).The telomerase avtivities of nasopharyngeal carcinaoma CD133+ stem cells and ECV cells were detected by Stretch PCR.The survival rates of CD133+stem cells and ECV cells were detected by  MTT method.Results After culture for 7 d in vitro,the number of nasopharyngeal carcinaoma CD133+ stem cells was increased, the tumorigenicity test of CD133+ stem cells  in vivo was positive.The telomerase activity of nasopharyngeal carcinaoma CD133+ stem cells was decreased after transfected by hTERTp/TK/pGL3 or CMV/TK/pGL3; the telomerase activity of EVC cells was negative.After transfected by TK/pGL3,CMV/TK/pGL3,and hTERTp/TK/pGL3,the  survival rates of CD133+ stem cells were 87.4％±0.4％,20.5％±0.4％,and 27.9％±0.2％,respectively. After transfected by TK/pGL3,CMV/TK/pGL3,and hTERTp/TK/pGL3,the  survival rates of ECV cells were 90.7％±0.1％,18.1％±0.2％,and 86.2％±0.1％,respectively.The efficiency of  hTERTp/TK/pGL3 vector  in  killing CD133+ stem cells was higher than that of  ECV cells（P<0.01）.Conclusion hTERTp/TK/pGL3 vector can targetedly inhibit the telomerase-positive nasopharyngeal carcinaoma CD133+ stem cells by down-regulation of telomerase activity.

Key words: nasopharyngeal neoplasms, CD133+tumor stem cells, targeted tumor therapy, telomerase