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目的研究组蛋白去乙酰化酶(HDAC)抑制剂曲古抑菌素A(TSA)与过氧化物酶体增殖物激活受体γ配体罗格列酮(ROZ)联合应用对胃癌细胞SGC-7901增殖的抑制作用,并探讨其可能的作用机制。方法首先用不同浓度的TSA和ROZ分别作用于SGC-7901细胞,MTT法检测二者对细胞增殖的抑制作用,以筛选出合适的联合作用浓度。将SGC-7901细胞随机分为对照组、TSA组、ROZ组和TSA+ROZ组,加入相应的药物处理48h后,MTT法检测各组细胞增殖抑制率,并应用流式细胞仪检测细胞周期情况,RT-PCR检测PPARγ和CyclinD1基因mRNA的转录水平。结果对SGC-7901细胞增殖抑制作用不显著的低剂量TSA(40nmol/L)与ROZ联用时,能显著增强ROZ对细胞增殖的抑制作用,TSA+ROZ组G0/G1期细胞比例较单用TSA或ROZ组明显增加,且CyclinD1基因mRNA转录水平明显下降;TSA作用于细胞后,PPARγ基因mRNA转录水平较对照组明显升高,而ROZ单独作用后,细胞PPARγ基因mRNA转录水平无改变。结论TSA可明显增强ROZ对SGC-7901细胞增殖的抑制效应,提示HDAC在SGC-7901细胞内可能具有抑制PPARγ的作用。
Objective To investigate the effects of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, and rosiglitazone (ROZ), a ligand of peroxisome proliferator-activated receptor γ, on the growth of gastric cancer cell SGC- 7901 proliferation inhibition and explore its possible mechanism of action. Methods SGC-7901 cells were treated with different concentrations of TSA and ROZ, respectively. MTT assay was used to detect the inhibitory effect of both on cell proliferation, so as to screen out the appropriate concentration of the combination. The SGC-7901 cells were randomly divided into control group, TSA group, ROZ group and TSA + ROZ group. After 48h treatment with corresponding drugs, the cell proliferation inhibition rate of each group was detected by MTT assay. Cell cycle was detected by flow cytometry The mRNA transcription levels of PPARγ and CyclinD1 were detected by RT-PCR. Results Low dose TSA (40 nmol / L) with no significant inhibitory effect on SGC-7901 cells proliferation could significantly enhance the inhibitory effect of ROZ on cell proliferation. The percentage of cells in G0 / G1 phase of TSA + ROZ group was significantly higher than that of TSA alone Or ROZ group, and the transcription level of CyclinD1 mRNA was significantly decreased. The transcription level of PPARγ mRNA was significantly increased after treated with TSA, while the mRNA level of PPARγ mRNA was not changed after ROZ treatment. Conclusion TSA can significantly enhance the inhibitory effect of ROZ on the proliferation of SGC-7901 cells, indicating that HDAC may inhibit the expression of PPARγ in SGC-7901 cells.