曲古抑菌素A抑制肿瘤细胞增殖及提高p21基因表达

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.

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

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 MTT 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.