X射线诱导NSCLC组织Axin表达并通过p53或JNK途径促进细胞凋亡

目的研究X-射线对非小细胞肺癌(non-smallcelllungcancer,NSCLC)组织中Axin表达的作用,以及X射线上调Axin表达的机制。方法应用Westernblot、RT-PCR方法检测15例经过X射线照射后NSCLC组织中Axin在蛋白水平及RNA水平的表达变化情况以及caspase-3活化情况。转染Axin及AxinΔp53ΔHIPK2至A549、BE1细胞中,并施加p53或JNK抑制剂,细胞经X线照射后用流式细胞仪(FCM)检测细胞凋亡,研究Axin上调细胞凋亡的机制。结果经X射线照射后,在15例NSCLC肺癌组织中,有8例Axin在RNA水平和蛋白水平上表达上调,与Axin未上调组相比,细胞凋亡显著增加(P<0.05)。转染Axin能使A549、BE1细胞凋亡明显增加,AxinΔp53ΔHIPK2不能上调A549细胞凋亡,p53抑制剂和JNK抑制剂分别抑制A549和BE1细胞凋亡。结论 X射线诱导部分NSCLC组织Axin表达增加并促进细胞凋亡,Axin通过p53或JNK途径促进X射线诱导的细胞凋亡。检测NSCLC组织中是否存在p53基因突变并不能作为判定是否对X射线敏感的指标。

X-ray upregulates Axin expression and induces apoptosis by p53/JNK pathway in NSCLC

Objective To study the effect of X-ray on the expression of Axin in non-small cell lung cancer（NSCLC） and the mechanism of X-ray up-regulating Axin.Methods Western blot and RT-PCR were performed to detect the expression of protein and RNA in 15 cases of NSCLC,Western blot and RT-PCR were used to detect the caspase-3 expression.Axin and AxinΔp53ΔHIPK2 were transfected into A549 and BE1 cells respectively,and the inhibitors of p53 and JNK were added to the transfected cells to block p53 and JNK apoptotic pathways.Results X-ray up-regulated the expression level of Axin mRNA and protein and the apoptosis rate in 8 cases of NSCLC tissues（0.05）.Transfected Aixn enhanced the apoptosis rate of A549 and BE1 cells,and transfected AxinΔp53ΔHIPK2 could not enhance the apoptosis rate of A549 cells.The inhibitors of p53 and JNK inhibited apoptosis of A549 and BE1 cells respectively.Conclusions X-ray up-regulates Axin in some NSCLC tissues and induces apoptosis.Axin promotes X-ray-induced apoptosis by p53 or JNK pathway.The p53 mutation status is not a good indicator for determining X-ray sensitivity in NSCLC cases.