TNF-α对白血病K562及K562/ADM细胞hTERT及mdr1表达的抑制作用  

Inhibitory effect of TNF-αon expression of hTERT and mdr1 gene in leukemic K562 and K562/ADM cell lines

作　　者：姜莉华[1] 初晶学[1] 孙善会[1] 刘洋[1] 黄平[2] 

机构地区：[1]济南市中心医院中心实验室,济南250013 [2]济南市中心医院 中心实验室,济南250013

出　　处：《中国肿瘤生物治疗杂志》2007年第5期477-480,共4页Chinese Journal of Cancer Biotherapy

摘　　要：目的：观察TNF—α对人髓系白血病细胞K562及其耐药细胞K562／ADM hTERT基因表达、端粒酶活性的抑制以及对多药耐药（muhidrug resistance—1，mdr1）基因表达的影响。方法：K562及K562／ADM细胞传代培养，加入5×10^6U／L的TNF-α培养24h进行诱导实验；MTT法检测K562和K562／ADM细胞的增殖能力，流式细胞术检测K562和K562／ADM细胞的凋亡，RT-PCR检测hTERT和mdr1 mRNA的表达，ELISA法检测端粒酶活性。结果：TNF—α诱导K562及K562／ADM细胞表现持续的生长抑制作用，且具有时效关系（P〈0．05）；TNF-α诱导K562及K562／ADM细胞的凋亡率增加（P〈0．05），而且耐药细胞K562／ADM凋亡的增加更明显（P〈0．01）；hTERT基因与端粒酶活性的表达密切相关（r=0．983，P〈0．05），TNF—α诱导后两者也同时下调（P〈0．01）；多药耐药mdr1基因伴随着hTERT基因的下调而下调（r=0．966，P〈0．05）。结论：TNF—α能诱导白血病K562及K562／ADM细胞系hTERT基因表达的抑制，端粒酶活性下调的同时多药耐药基因mdr1的表达也下调。Objective： To investigate the inhibitory effect of TNF-α on hTERTgene expression in human myelogenous leukemia cell line K562 and K562/ADM and to study the influence of changed telomerase activity on expression of multidrug resistance-1 （mdr1） gene. Methods： K562 and K562/ADM cells were treated with 5× 10^6U/L TNF-α for 24 h, then cell proliferation was detected by MTr assay and cell apoptosis was detected by flow cytometry. The expression of hTERT and mdrl mRNA was detected by RT-PCR and the telomerase activity was detected by ELISA. Results： TNF-α inhibited the growth of K562 and K562/ADM cells and the inhibition showed a time-effect relationship （ P 〈 0.05 ）. TNF-St also significantly increased the apoptosis rates of K562 and K562/ADM cells （ P 〈 0.05 ）, with the increase in drug-resistant K562/ADM cells more significantly （ P 〈 0.01 ） . hTERT gene expression was correlated with telomerase activity （ Pearson correlation coefficient r = 0. 983, P 〈 0.05 ）. TNF-α treatment decreased hTERT expression and telomerase activity. Mdrl gene expression decreased with the decrease of hTERT gene （ r = 0.966, P 〈 0.05 ）. Conclusion： TNF-α can inhibit the expression of hTERT gene in human K562 and K562/ADM cells ; the down-regulation of telomerase activity is accompanied by the down-regulation of mdr1 gene expression.

关 键 词：人端粒酶逆转录酶 TNF—α 白血病 

分 类 号：R733.7[医药卫生—肿瘤] R730.5[医药卫生—临床医学]