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


CONCLUSIONS
TSA induces the expression of P21WAF1/CIP1 through inhibition of HADC3.
Wang
Chun-ting
CT
Intensive Care Unit, Shandong Provincial Hospital, Jinan 250021, China.
Meng
Mei
M
D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099186:Histone Deacetylase 3
D050759:Cyclin-Dependent Kinase Inhibitor p21; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D012333:RNA, Messenger; D000099186:Histone Deacetylase 3; C493956:CDKN1A protein, human; C012589:trichostatin A