曲古抑菌素A对人肺癌细胞分化作用的实验研究

[Experimental study on the effect of trichostatin A on differentiation of human lung carcinoma cell].

作者信息

Wang Chun-ting, Meng Mei

机构信息

Intensive Care Unit, Shandong Provincial Hospital, Jinan 250021, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2007 Apr 3;87(13):927-9.

PMID:17650409

Abstract

OBJECTIVE

To investigate the influence of trichostatin A (TSA) on the proliferation and phase growth arrest of human lung carcinoma cells and on the expression of histone deacetylase 3 (HDAC3).

METHODS

Human lung carcinoma cells of the line A549 were cultured and treated with TSA of the concentrations of 5, 10, 20, and 40 microg/L. MTT assay was adopted to observe the proliferation of the cells. The cell cycle was determined by flow cytometry. RT-PCR was used to determine the mRNA expression of P21WAF1/CIP1 gene, a tumor suppressor gene, and histone deacetylase 3 (HDAC3) in the A549 cells.

RESULTS

Trichostatin A treatment led to a time- and dose-dependent inhibition in carcinoma cells A549 proliferation (Twenty-four hours after the treatment of TSA The inhibition rates of the A549 cells in the control group and the cells treated with TSA of the concentrations of 5, 10, 20, and 40 microg/L were 6.2%+/-1.1%, 18.5%+/-2.3%, 28.9%+/-3.6%, 39.4%+/-3.7%, and 45.6%+/-2.7% respectively 24 hours later (P<0.05): 8.1%+/-2.3%, 26.9%+/-4.2%, 35.6%+/-3.8%, 56.5%+/-6.1%, and 69.8%+/-5.3% 48 h later (P<0.05); and 10.5%+/-1.3%, 28.4%+/-3.2%, 50.5%+/-5.8%, 70.5%+/-6.9%, and 78.6%+/-4.5% 72 h later (P<0.05). The percentages of the cells in the G0/G1 phase of the control group and the groups treated by TSA of different concentrations were 56.5%+/-8.1%, 70.5%+/-6.7%, 78.6%+/-4.6%, 82.4%+/-3.7%, and 85.6%+/-7.5% respectively (P<0.05). The mRNA expression of HDAC3 of the control group and the TSA-treated groups were 0.85, 052, 0.43, 0.32, and 0.25 respectively, P<0.05), and the mRNA expression of P21WAF1/CIP1 were 0.09, 0.17, 0.20, 0.27, and 0.35 respectively, P<0.05).

CONCLUSION

TSA induces the expression of P21WAF1/CIP1 through inhibition of HADC3.

摘要

目的

探讨曲古抑菌素A（TSA）对人肺癌细胞增殖、细胞周期生长阻滞及组蛋白去乙酰化酶3（HDAC3）表达的影响。

方法

培养人肺癌A549细胞株，分别用浓度为5、10、20和40μg/L的TSA处理。采用MTT法观察细胞增殖情况。通过流式细胞术检测细胞周期。运用RT-PCR法检测A549细胞中抑癌基因P21WAF1/CIP1及组蛋白去乙酰化酶3（HDAC3）的mRNA表达。

结果

曲古抑菌素A处理导致A549癌细胞增殖呈时间和剂量依赖性抑制（TSA处理24小时后，对照组及分别用5、10、20和40μg/L TSA处理的细胞的抑制率分别为6.2%±1.1%、18.5%±2.3%、28.9%±3.6%、39.4%±3.7%和45.6%±2.7%；24小时后（P<0.05）：8.1%±2.3%、26.9%±4.2%、35.6%±3.8%、56.5%±6.1%和69.8%±5.3%；48小时后（P<0.05）；10.5%±1.3%、28.4%±3.2%、50.5%±5.8%、70.5%±6.9%和78.6%±4.5%；72小时后（P<0.05）。对照组及不同浓度TSA处理组处于G0/G1期的细胞百分比分别为56.5%±8.1%、70.5%±6.7%、78.6%±4.6%、82.4%±3.7%和85.6%±7.5%（P<0.05）。对照组及TSA处理组HDAC3的mRNA表达分别为0.85、0.52、0.43、0.32和0.25，P<0.05），P21WAF1/CIP1的mRNA表达分别为0.09、0.17、0.20、0.27和0.35，P<0.05）。