曲古抑菌素A抑制肿瘤细胞增殖及提高p21基因表达  

Trichostatin A inhibits proliferation of human tumor cell and induces expression of p21

作　　者：徐周敏[1] 梅琪[1] 陈坚[1] 杜佳[1] 魏燕[1] 徐迎春[1] 

机构地区：[1]武警上海总队医院血液肿瘤科,上海201103

出　　处：《军事医学科学院院刊》2007年第5期420-422,共3页Bulletin of the Academy of Military Medical Sciences

摘　　要：目的:探讨组蛋白乙酰化酶抑制剂曲古抑菌素A(TSA)对人肿瘤细胞的杀伤作用和机制。方法:选用3种人肿瘤细胞株,即白血病细胞株HL-60、非小细胞肺癌细胞株A549、乳癌细胞株MCF-7,采用MTT法检测TSA作用后肿瘤细胞的增殖状态;用流式细胞仪定量分析肿瘤细胞增殖周期的改变;用半定量RT-PCR法测定细胞周期相关基因p21的表达。结果:TSA能有效抑制肿瘤细胞的增殖,呈剂量依赖性;在接近各细胞IC50浓度的TSA作用下,可使肿瘤细胞主要阻滞在G2/M期,而S期细胞明显减少;TSA作用48 h内即可引起细胞周期相关基因p21的表达显著增强。结论:TSA在体外能有效抑制多种人肿瘤细胞的生长,具有广谱抗肿瘤效应;其抗肿瘤生长机制可能是通过细胞周期阻滞和上调p21基因表达水平实现的。Objective： To investigate the antitumor activity and mechanism of trichostatin A （TSA）. Methods：A human leukemia cell line HL-60, a human lung cancer cell line A549 and a breast cancer cell line MCF-7 were exposed to TSA. Cell proliferation was assessed by the MTr assay, cell cycle by flow cytometry and the expression of p21 gene by semiquantitative RT-PCR. Results： MTT assay showed that all tumor cell lines were sensitive to the growth inhibitory effect of TSA. Cell cycle analysis indicated that the proportion of cells in S phase was decreased and the proportion of cells in the G2/M phases was increased after treatment with TSA. The up-regulation of p21 expression was observed within 48 h after the treatment. Conclusions： These results suggest that TSA is effective in inhibiting growth of human tumor cell in vitro. The findings raise the possibility that TSA may be particularly effective in treatment of tumors.

关 键 词：肿瘤 组蛋白去乙酰化酶抑制剂 曲古抑菌素A P21基因 细胞周期 

分 类 号：R96[医药卫生—药理学]