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LASS2 interacts with V-ATPase and inhibits cell growth of hepatocellular carcinoma
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- Author:
- No author available
- Journal Title:
- ACTA PHYSIOLOGICA SINICA
- Issue:
- 3
- DOI:
- No doi available
- Key Word:
- 人源性长寿保障基因2;肝癌;细胞生长;凋亡;细胞色素c
Abstract： 人源性长寿保障基因2(Homo sapiens longevity assurance homologue 2,LASS2)是本实验室克隆到的一个与酵母长寿保障基因LAG1高度同源的人类新基因.前期研究显示,LASS2可与V-ATPase质子泵的c亚基ATP6L结合,过表达LASS2可以抑制肝癌细胞SMMC-7721的生长.本研究旨在探讨LASS2对V-ATPase质子泵功能的调节是否参与LASS2对肝癌细胞生长的抑制作用.使用本室构建、保存的pCMV-HA2-LASS2质粒瞬时转染肝癌细胞(HCCLM3),而未转染质粒的HCCLM3细胞作为空白对照,运用CCK-8试剂盒检测细胞生长情况;采用BCECF-AM和BCECF氢离子敏感探针分别测定细胞内、外H+浓度;应用流式细胞仪检测细胞凋亡;Western blot检测线粒体和胞质内细胞色素c(cytochrome c,Cyt c)、胞质中的无活性pro-caspase-3的表达情况.结果显示,外源性LASS2的过表达对HCCLM3细胞生长有抑制作用:过表达LASS2使HCCLM3细胞内H+浓度上升,细胞凋亡率提高,线粒体Cyt c释放增加,胞质中pro-caspase-3含量下降.以上结果提示提示LASS2可能通过调控V-ATPase质子泵的功能,提高细胞内H+浓度,从而激活细胞线粒体凋亡途径、抑制肝癌细胞的生长.
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