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首页> 外文期刊>Cell biology international. >Aplasia Ras homologue member I overexpression induces apoptosis through inhibition of survival pathways in human hepatocellular carcinoma cells in culture and in xenograft.
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Aplasia Ras homologue member I overexpression induces apoptosis through inhibition of survival pathways in human hepatocellular carcinoma cells in culture and in xenograft.

机译:发育不全的Ras同源成员I的过度表达通过抑制培养物中和异种移植物中人肝癌细胞的存活途径来诱导凋亡。

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摘要

The aim of the present study was to determine the effects of ARHI (aplasia Ras homologue member I; also known as DIRAS3), a member of the Ras superfamily, on HCC (hepatocellular carcinoma) cells and to define the molecular pathways involved. Stable transfection of ARHI into the HCC cell line Hep3B that lacks expression of this gene reduced cell proliferation significantly as compared with the transfection of empty vector (P<0.01). Moreover, the re-expression of ARHI induced significant apoptosis, whereas a few vector transfectants or non-transfected cells displayed apoptosis. Mechanistically, ARHI restoration impeded the activation of both Akt (also called protein kinase B) and NF-kappaB (nuclear factor kappaB). In vivo, restoring ARHI also exerted suppressive effects on xenograft tumour growth, which was coupled with increased apoptosis. Together, these results indicate that ARHI has pro-apoptotic effects on HCC cells, which is associated with the inactivation of both Akt and NF-kappaB survival pathways.
机译:本研究的目的是确定ARHI(Ras超家族成员Ilaslas Ras的同系物I;也称为DIRAS3)对HCC(肝细胞癌)细胞的作用并确定涉及的分子途径。与空载体转染相比,ARHI稳定转染到缺乏该基因表达的HCC细胞系Hep3B中,细胞增殖明显降低(P <0.01)。而且,ARHI的重新表达诱导了显着的细胞凋亡,而一些载体转染子或未转染的细胞显示出细胞凋亡。从机理上讲,ARHI的恢复阻碍了Akt(也称为蛋白激酶B)和NF-kappaB(核因子kappaB)的激活。在体内,恢复ARHI还对异种移植肿瘤的生长产生抑制作用,并伴有凋亡增加。总之,这些结果表明,ARHI对HCC细胞具有促凋亡作用,这与Akt和NF-kappaB生存途径的失活有关。

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