肿瘤抑制基因LZTS1通过损害PI3K/Akt信号通路抑制肝细胞癌增殖。

The tumor-suppressor gene LZTS1 suppresses hepatocellular carcinoma proliferation by impairing PI3K/Akt pathway.

作者信息

He Yonghong, Liu Xia

机构信息

Department of Gastroenterology, Fengcheng Hospital, Shanghai, China.

出版信息

Biomed Pharmacother. 2015 Dec;76:141-6. doi: 10.1016/j.biopha.2015.10.006. Epub 2015 Nov 18.

DOI:10.1016/j.biopha.2015.10.006

PMID:26653561

Abstract

BACKGROUND

To study the role of LZTS1 in hepatocellular carcinoma (HCC) proliferation and the molecular mechanism involved.

METHODS

LZTS1 expression was studied in 10 HCC cell lines and 1 normal hepatocyte cell line by western blot analysis and qRT-PCR. One HCC cell line was selected and transfected with LZTS1 lentivirus. Cell proliferation and cell cycle were then determined by CCK-8 assay and flow cytometry, respectively. LZTS1, cyclin D1, CDK1, Cdc25C, pS473 Akt, and pT308 Akt mRNA and protein expressions were measured. PS473 Akt and pT308 Akt expression level was also compared with the HCC cells treated with LY294002.

RESULTS

Compared with the normal hepatocyte cells, LZTS1 expression in HCC cells was significantly lower. After the transfection with LZTS1 lentivirus, HCC cell proliferation ability decreased markedly and HCC cells were blocked at G2/M phase. Cyclin D1 and CDK1 expression were both decreased but not significantly. Cdc25C expression was increased significantly. PS473 Akt and pT308 Akt expression level was increased significantly as well, which were almost the same with those transfected with LY294002.

CONCLUSION

LZTS1 could inhibit HCC cell proliferation by impairing PI3K/Akt pathway.

摘要

背景

研究LZTS1在肝细胞癌（HCC）增殖中的作用及相关分子机制。

方法

通过蛋白质免疫印迹分析和定量逆转录聚合酶链反应（qRT-PCR）研究10种肝癌细胞系和1种正常肝细胞系中LZTS1的表达。选择一种肝癌细胞系并用LZTS1慢病毒转染。然后分别通过CCK-8法和流式细胞术测定细胞增殖和细胞周期。检测LZTS1、细胞周期蛋白D1、细胞周期蛋白依赖性激酶1（CDK1）、细胞分裂周期蛋白25C（Cdc25C）、磷酸化丝氨酸473的蛋白激酶B（pS473 Akt）和磷酸化苏氨酸308的蛋白激酶B（pT308 Akt）的mRNA和蛋白表达。还将pS473 Akt和pT308 Akt的表达水平与用LY294002处理的肝癌细胞进行比较。

结果

与正常肝细胞相比，肝癌细胞中LZTS1的表达明显降低。用LZTS1慢病毒转染后，肝癌细胞增殖能力明显下降，且肝癌细胞停滞于G2/M期。细胞周期蛋白D1和CDK1的表达均降低，但差异不显著。Cdc25C的表达显著增加。pS473 Akt和pT308 Akt的表达水平也显著增加，与用LY294002转染的细胞几乎相同。