Neutral lactate promotes proliferation, migration and invasion of hepatocellular carcinoma cells by activating pi3k/akt signaling pathway / 肿瘤

ABSTRACT

Objective: To investigate the effects of neutral lactate on the proliferation, migration and invasion of hepatocellular carcinoma (HCC) cells, and to explore its possible molecular mechanism. Methods: The HCC SMMC-7721 and HepG2 cells were treated with 0 (as the control), 2.5, 5 and 10 mmol/L neutral lactate, respectively. Then the proliferation of HCC cells was detected by MTT assay. The migration and invasion abilities of HCC cells were detected by Transwell chamber method. The expression levels of phosphoinositide 3-kinase (PI3K), protein kinase B (PBK, Akt), phospho-Akt (Ser473) [p-Akt (S473)], matrix metallopeptidase-2 (MMP-2) and MMP-9 were detected by Western blotting. The HCC cells SMMC-7721 and HepG2 were divided into four groups, and treated with equal volume of medium (as the control), neutral lactate, perifosine (an inhibitor of PI3K/Akt pathway), and neutral lactate combined with perifosine, respectively. Then MTT assay and Transwell chamber assay were used to detect the proliferation, migration and invasion abilities of HCC cells in each group. The expression levels of PI3K, Akt, p-Akt (S473), MMP-2 and MMP-9 proteins in HCC cells were detected by Western blotting. Results: The proliferation, migration and invasion abilities of SMMC-7721 and HepG2 cells in 5 and 10 mmol/L neutral lactate treatment groups were significantly enhanced as compared with the control group (all P < 0.01). The expression levels of PI3K, p-Akt (S473), MMP-2 and MMP-9 proteins in HCC cells treated with neutral lactate were significantly increased as compared with the control group (all P < 0.01). Compared with the control group, the proliferation, migration and invasion abilites of HCC cells in the perifosine treatment group were significantly decreased (all P < 0.05), and the expression levels of PI3K, p-Akt (S473), MMP-2 and MMP-9 proteins were also significantly down-regulated (all P < 0.05). Compared with the neutral lactate treatment group, the proliferation, migration and invasion abilities of HCC cells in the neutral lactate combined with perifosine treatment group were significantly reduced (all P < 0.01), and the expression levels of PI3K, p-Akt (S473), MMP-2 and MMP-9 proteins were significantly decreased (all P < 0.01). Conclusion: Neutral lactate promotes the proliferation, migration and invasion of HCC cells by activating PI3K/Akt pathway, while the PI3K/ Akt inhibitor perifosine can significantly reduce the stimulative effects of neutral lactate on the proliferation, migration and invasion of HCC cells.