多西紫杉醇对人胃癌细胞BGC-823 hTERT启动子转录活性及其调控基因c-myc表达的研究  

Repression of hTERT promoter and c-myc by docetaxel in human gastric carcinoma BGC-823 cells

作　　者：蒋谦[1] 陈环球[1] 周晓明[2] 何晓松[2] 戴美红[2] 俞军[2] 

机构地区：[1]江苏省肿瘤医院普外科,江苏南京210009 [2]江苏省肿瘤医院科研科,江苏南京210009

出　　处：《中华肿瘤防治杂志》2007年第20期1531-1534,共4页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的:探讨多西紫杉醇对人胃癌细胞BGC-823端粒酶活性和端粒酶逆转录酶(hTERT)mRNA表达、hTERT启动子转录活性及其转录调控基因c-myc蛋白表达的影响。方法:加药多西紫杉醇24、48和72h后收集细胞,MTT比色法测定IC50值;分别采用PCR-ELISA法检测端粒酶活性和RT-PCR法检测端粒酶逆转录酶hTERT mRNA的表达;Luciferase法检测hTERT启动子活性;Western blot技术检测c-myc蛋白的表达。结果:多西紫杉醇可以明显抑制胃癌细胞BGC-823的端粒酶活性和hTERT mRNA的表达,呈一定的时效、量效关系;进一步研究发现,多西紫杉醇对胃癌细胞端粒酶活性的影响抑制了hTERT启动子转录活性的表达,同时对启动子转录活性调控蛋白c-myc表达的研究也证实了这一点。结论:hTERT mRNA的表达与胃癌的发生和演进有关,癌基因c-myc可能通过参与hTERT启动子转录活性的表达调控而调控hTERT mRNA表达。多西紫杉醇抑制胃癌细胞BGC-823的增殖可能与其抑制BGC-823细胞hTERT启动子转录活性和c-myc蛋白表达相关。OBJECTIVE： To study the effect of docetaxel to hTERT promoter and c-myc in human gastric carcinoma BGC-823 cells. METHODS： Further molecular mechanisms of inhibition of hTERT caused by docetaxel at 24, 48 and 72 hours were investigated by using BGC-823 human docetaxelstric carcinoma cells. In vitro inhibition of BGC-823 cells was measured by MTT assay, and the reverse transcriptase-PCR and hTERT promoter activity assays were also used. RESULTS： Docetaxel decreased hTERT expression and transcriptional activity time- and dose-dependently. Moreover, a time-and dose-dependent decrease in c-myc proteins was observed after docetaxel treatment detected by Western blot. Docetaxel repressed hTERT transcriptional activity via the down regulation of c-myc expression. However, docetaxel-induced repression of hTERT transcriptional activity was blocked by the c-myc at the hTERT promoter. CONCLUSION： Docetaxel represses telomerase activity in human gastric carcinoma cells 823 by repressing hTERT transcriptional activity via c-myc.

关 键 词：胃肿瘤/药物疗法 紫杉醇/药理学 基因 C-MYC 

分 类 号：R735.2[医药卫生—肿瘤]