食道癌细胞在异鼠李素处理中应激作用的研究

The study on cellular stress response in isorhamnetin-treated Eca-109 cells

在前期研究的基础上,探究异鼠李素抑制食道癌细胞增殖作用过程中出现的细胞应激反应的分子机制.将食道癌Eca-109细胞经异鼠李素处理后,在前72h细胞出现持续增殖.前期细胞核内NF-κB/p65和NF-κB/p50的表达上升而后期逐渐降低;bcl-2、COX-2、mcl-1基因的表达在前期上调,后期下调;IκBα和bax的表达先下降而后上升;加入MG-132后NF-κB/p50和NF-κB/p65的核内表达明显降低,Eca-109细胞增殖受到抑制,在前72h细胞未出现持续快速增殖现象.表明在异鼠李素处理前期,通过食道癌细胞应激作用激活NF-κB信号途径,导致下游相关基因的表达变化从而抑制异鼠李素诱导Eca-109细胞的凋亡作用,而在处理后期异鼠李素诱导的细胞毒性作用占主导地位,导致NF-κB信号途径及食道癌细胞增殖被抑制.

To explore the molecular mechanisms of cellular stress response in the isorhamnetintreated Eca-109 cells on the basis of the previous research in our lab. Data showed that the proliferation of Eca- 109 cells was not absolutely arrested initially but still continued proliferation within the 72 h when these cells were exposed to isorhamnetin. It was found that the expression levels of NF-κB/p65 and NF-κB/ pS0 were increased in nuclei at first. The expressions of COX-2, bcl-2 and rncl-1 were up-regulated with the treatment of isorhamnetin at first. IκBa and Bax were down-regulated initially but then up-regula- ted. After treated with MG-132 additionally, the nuclei expressions of p50/p65 were decreased and the proliferation of isorhamnetin-treated Eca-109 cells within the initial 72 h was inhibited. In conclusion, during the initial exposure to isorhamnetin, cellular stress response activated NF-κB signaling pathway, then changed the expression levels of the downstream gene expression to inhibit the apoptosis induced by isorhamnetin in the initial 72 h. But then the apoptosis induced by isorhamnetin plays a dominant role, which inhibits the NF-κB pathway and the proliferation of Eca-109 cells.