组蛋白去乙酰酶抑制剂对结肠癌细胞增殖和ID4基因表达的影响  

Effects of histone deacetylase inhibitor on colon cancer cell growth and ID4 gene expression

作　　者：张波[1] 陈剑英[1] 王国斌[1] 陈道达[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院普外科,湖北省武汉市430022

出　　处：《世界华人消化杂志》2007年第18期2021-2025,共5页World Chinese Journal of Digestology

摘　　要：目的:研究组蛋白去乙酰酶抑制剂曲古菌素A (TSA)对结肠癌细胞Caco2增殖的影响和机制.方法:5-500μg/L TSA处理结肠癌Caco2细胞0-5d,在药物处理前及36h后用MTT法检测细胞增殖状况.流式细胞仪检测细胞周期的改变.RT-PCR检测ID4 mRNA的表达.结果:TSA在100μg/L浓度以上可以明显抑制结肠癌Caco2细胞的增殖(P<0.05),但在5和20μg/L浓度时抑制作用不明显.100μg/L TSA可导致细胞G_1期阻滞,但没有诱导明显的细胞凋亡.RT-PCR显示20μg/L TSA作用36 h后ID4 mRNA表达增强(P<0.05),在100μg/L其表达显著增强(P<0.01).结论:TSA可以通过阻滞Caco2细胞的G_1期和重新表达ID4来发挥抑癌作用.AIM： To investigate whether Trichostatin A （TSA） possesses anti-tumor activity against human colon cancer cells. METHODS： The human colon cancer cell line Caco2 was treated with different concentrations of TSA, a potent and specific histone deacetylase inhibitor, for 0 to 5 d. The growth of Caco2 cells was observed by MTT assay before and after TSA treatment. The Caco2 cell cycle was analyzed by flow cytometry. The expression of ID4 mRNA was observed by reverse transcription- polymerase chain reaction. RESULTS： Trichostatin A in a dose-dependent fashion significantly inhibited the proliferation of colon cancer cells at 100 μg/L （P 〈 0.05）, The inhibition rate increased sharply from day 3 to 5 （57.3% to 70.2%）. TSA treatment induced cell cycle arrest at the G1 phase but did not increase apoptotic cell death as shown by flow cytometry. ID4 mRNA was expressed in Caco2 cells after 20 μg/L TSA treatment, but it was only weakly detectable before treatment. CONCLUSION： Our results demonstrated that TSA inhibited colon cancer cell growth in vitro, possibly through G1 cell cycle arrest and reexpression of the ID4 gene. This study suggested that TSA may be a potential therapeutic agent for the treatment of colon cancer.

关 键 词：组蛋白去乙酰酶抑制剂 结肠癌 ID4基因 

分 类 号：R735.35[医药卫生—肿瘤]