Distinct roles of Akt1 in regulating proliferation, migration and invasion in HepG2 and HCT 116 cells
Distinct roles of Akt1 in regulating proliferation, migration and invasion in HepG2 and HCT 116 cells
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Akt1 在调节 HepG2 和 HCT 116 细胞增殖、迁移和侵袭中的独特作用。
DOI：
10.3892/or.2013.2879
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发表时间：
2014-02-01
期刊：
影响因子：
4.2
通讯作者：
Wang, Chao-Jie
中科院分区：
文献类型：
--
作者：
Chen, Liang;Kang, Qiao-Hui;Wang, Chao-Jie
阐明参与肿瘤的基因的作用可能会改善人类癌症的治疗策略。近年来，一些研究发现，Akt 1在介导细胞增殖、迁移和侵袭方面发挥双重作用，这取决于细胞类型。然而，Akt 1在肝细胞癌（HCC）和结直肠癌细胞中的病理生理作用仍然知之甚少。在本研究中，我们将Akt 1表达质粒转染到仅表达低水平Akt 1的肿瘤细胞中。在24孔Boyden小室中分析了该菌的迁移和入侵能力。Western blot分析蛋白表达。我们的结果表明，Akt 1的过表达显着提高HepG 2和HCT 116细胞的增殖率和促进殖民地形成。当用渥曼青霉素处理时，在两种细胞系中形成集落的能力显著减弱。值得注意的是，Akt 1的增强表达诱导HepG 2细胞迁移和侵袭;相反，Akt 1表达的上调抑制HCT 116细胞的迁移和侵袭。随后的机制研究表明，Akt 1的上调显着诱导Bcl-2和NF-B在两种类型的肿瘤细胞的表达。值得注意的是，我们在HCC细胞中观察到MMP 2、MMP 9、HIF 1和VEGF的类似增加，而Akt 1显著抑制这些分子在结直肠癌细胞中的表达。这些数据表明Akt 1在肿瘤细胞迁移和侵袭中的双重作用，并突出了Akt 1激酶在细胞运动调节中的细胞类型特异性作用。
Elucidating the effects of genes involved in tumors may improve therapeutic strategies for human cancer. Recently, several studies discovered that Akt1 plays a dual role in mediating cell proliferation, migration and invasion, depending on the cell type. However, the pathophysiological role of Akt1 in hepatocellular carcinoma (HCC) and colorectal carcinoma cells remains poorly understood. In the present study, we transfected the Akt1-expressing plasmids into the tumor cells that expressed only low levels of Akt1. The migration and invasion abilities were analyzed in 24-well Boyden chambers. The expression of proteins was detected using western blot analysis. Our results demonstrated that overexpression of Akt1 significantly enhanced the proliferation rates and promoted the colony formation in both HepG2 and HCT 116 cells. When treated with wortmannin, the ability to form colonies was significantly attenuated in both cell lines. Of note, enforced expression of Akt1 induced HepG2 cell migration and invasion; by contrast, upregulation of Akt1 expression suppressed the migration and invasion of HCT 116 cells. Subsequent mechanistic investigations revealed that upregulation of Akt1 markedly induced the expression of Bcl-2 and NF-B in both types of tumor cells. Notably, we observed a similar increase of MMP2, MMP9, HIF1 and VEGF in HCC cells, whereas Akt1 significantly suppressed the expression of these molecules in colorectal carcinoma cells. These data suggest a dual role for Akt1 in tumor cell migration and invasion and highlight the cell type-specific actions of Akt1 kinases in the regulation of cell motility.