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曲古菌素A抑制乳腺癌细胞增殖的分子机制 被引量:4

Molecular mechanisms of Trichostatin A inhibiting the proliferation of breast cancer cells
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摘要 目的研究组蛋白去乙酰酶抑制剂-曲古菌素A(TSA)对乳腺癌T47D细胞增殖的影响和机制。方法不同浓度的TSA作用乳腺癌T47D细胞5 d,噻唑蓝(MTT)法检测药物作用前后细胞增殖的情况。流式细胞仪检测TSA作用36 h后细胞周期的改变。逆转录-聚合酶链反应(RT- PCR)检测TSA作用36 h后Maspin mRNA的表达。结果TSA在20μg/L浓度以上可以明显抑制乳腺癌T47D细胞的增殖,并呈现剂量和时间的依赖性。细胞周期检测发现100μg/L TSA可导致细胞G_1期阻滞,并诱导细胞凋亡;而500μg/L TSA可显著的诱导细胞凋亡。RT-PCR显示100μg/ L TSA作用36 h后Maspin mRNA的表达增强,但在20μg/L时其表达与对照组差异无统计学意义。结论TSA可以抑制乳腺癌T47D细胞的生长,可能通过诱导细胞凋亡和Maspin基因的重新表达发挥抑癌作用。TSA可能是乳腺癌治疗的潜在靶点。 To investigate whether Trichostatin A (TSA) possesses anti-tumor activity against human breast cancer cells. Methods Human breast cancer cell line T47D was treated with different concentrations of TSA, a potent and specific histone deacetylase inhibitor for 0 to 5 days. The growth of T47D cells was observed by MTT assay before and after TSA treatment. The cell cycle of T47D cells was analyzed by flow cytometry. The expression of Maspin mRNA was detected by reverse transcriptionpolymerase chain reaction (RT-PCR). Results TSA significantly inhibited the proliferation of breast cancer cell in a doseand time-dependent manner when the concentration was above 20 μg/L. The inhibition rate of 100 μg/L TSA treatment was increased sharply from day 2 to 5 (46.17% to 73.01% ). 100 lag/L TSA treatment could also induce cell cycle arrest at the G1 phase and increase apoptosis. Maspin mRNA was expressed in T47D cells after 100 μg/L TSA treatment, but it was weakly detectable at 20 μg/L TSA and control group. Conclusion TSA can inhibit breast cancer cell growth in vitro, possibly through G1 cell cycle arrest and induction of re-expression of Maspin gene. This study suggests that TSA may be a potential therapeutic agent for the treatment of breast cancer.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2007年第10期1192-1194,共3页 Chinese Journal of Experimental Surgery
基金 湖北省"十一"五重大科技攻关项目(2006AA301A05)
关键词 曲古菌素A 乳腺癌 基因表达 Trichostatin A Breast carcinoma Gene expression
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