姜黄素对胃癌细胞P300、P53、c-myc及乙酰化组蛋白H3和H4表达的影响

The Effect of Curcumin on Expression of P300,P53,c-myc and Acetyl Histone H3,H4 in the Gastric Cancer Cell

目的了解姜黄素对胃癌细胞P300、P53、c-myc以及乙酰化组蛋白H3和H4表达的影响,探讨其抗胃癌的分子机制。方法用不同浓度的姜黄素作用人胃腺癌细胞系SGC-7901,作用24、48 h后,Rt-PCR法检测P300、P53c、-myc mRNA的表达;蛋白免疫印迹法检测乙酰化组蛋白H3、H4、P300、P53、c-myc蛋白的表达。结果在胃癌细胞SGC-7901中P300和c-myc的表达随姜黄素浓度的改变而改变,在20μmol/L 24 h时抑制作用较为明显,且两者具有相关性(r=0.976),而野生型p53则没有明显变化;姜黄素对乙酰化的组蛋白H3、H4都有抑制作用。也以20μmol/L 24 h的作用最强。结论姜黄素能抑制P300表达,进而抑制组蛋白H3和H4的乙酰化以及原癌基因c-myc的表达,但不影响抑癌基因P53的表达。提示姜黄素抑制组蛋白乙酰化酶P300可能是其抗癌的分子机制之一。

Objective To investigate the effect of curcumin on expression of P300,P53, c - myc and acetyl histone H3, H4 and their molecular mechanism of anticancer in vitro. Methods The gastric cell line SGC - 7901 were treated with cureumin in different concentration. The expression of P300, P53, c - myc mRNA were assayed by reverse transcriptase polymerase chain reaction（ Rt- PCR）. The expression of acetyl histone H3 and H4, P300, P53 and c - myc protein were tested by western blot. Results The expression of P300, c - myc protein and mRNA was decreased sharply in SGC - 7901 cell treated with curcumin in different concentration, and the level was followed by the concentration of cureumin , which was inhibited most obviously with curcumin in 20 μmol/L 24 h. However, the expression of wide - type P53 protein and mRNA was not affected. Cureumin could inhibit the expression of acetyl histone H3 and H4 protein,which was the strongest in 20 μmol/L 24 h. Conclusion Cureumin can inhibit the expression of P300. Furthermore, the expression of oncogen c - myc and acetyl histone H3 and H4 protein can be decreased with it, but the expression of anti - oncogen P53 can not be decreased. Our study may imply that curcumin can treat cancer by inhibiting the expression of P300, which may be one of its molecular mechanism of anticancer.