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目的初步筛选不同p53表达型肺癌细胞株对曲古抑菌素A(TSA)敏感性不同的影响因素。方法分别以体外药物敏感试验(MTT法)、流式细胞术观察TSA处理3种肺癌细胞株(H1299为p53缺失型,H322为p53变异型,A549为p53野生型)后,其生长抑制情况以及细胞周期、细胞凋亡等指标的变化;用Western blot法检测3种细胞的人类表皮生长因子受体2(HER2)表达水平。结果TSA对3种细胞均有抑制作用,在96h时对A549的IC50抑制作用明显低于对H1299和H322的IC50(P<0.05),A549细胞凋亡也明显多于H1299和H322的细胞凋亡(P<0.05)。3种细胞株HER2蛋白表达水平由高到低依次为H322、A549和H1299,与TSA的IC50值之间无相关性。结论TSA对p53不同表达型人肺腺癌细胞株均有生长抑制作用,肺腺癌细胞株p53的不同表达型可能对TSA的敏感性产生影响,而HER2的表达强度不影响TSA的敏感性。
Objective To screen different influencing factors on the sensitivity of different p53-expressing lung cancer cell lines to trichostatin A (TSA). Methods MTT assay and flow cytometry were used to observe the growth inhibition of the three lung cancer cell lines treated with TSA (H1299 was p53-deficient, H322-p53-mutant and A549 was p53 wild-type) Cell cycle, apoptosis and other indicators of changes; using Western blot detection of three kinds of cells, human epidermal growth factor receptor 2 (HER2) expression levels. Results TSA had inhibitory effect on all three kinds of cells. The IC50 of A549 at 96 hours was significantly lower than that of H1299 and H322 at IC50 (P <0.05). The apoptosis of A549 cells was also significantly more than that of H1299 and H322 cells (P <0.05). The expression levels of HER2 in the three cell lines were H322, A549 and H1299 in descending order, but not correlated with the IC50 of TSA. Conclusion TSA inhibits the growth of human lung adenocarcinoma cells with different p53 expression. The different expression of p53 in lung adenocarcinoma cell line may affect the sensitivity of TSA, but the intensity of HER2 does not affect the sensitivity of TSA.