VLCAD inhibits the proliferation and invasion of hepatocellular cancer cells through regulating PI3K/AKT axis

Purpose Very-long-chain acyl-CoA dehydrogenase (VLCAD) is an essential mediator in fatty acid metabolism. The progression of human hepatocellular carcinoma (HCC) is closely associated with the disorder of energy supply. Here, we aimed to investigate the role and underlying molecule mechanism of VLCAD in pathological process of HCC. Methods In this study, VLCAD was induced silencing and overexpression using small hairpin RNA (shRNA) and lentiviral-mediated vector in HCC cell lines. The proliferation of HCC cells was determined using CCK-8 assay. Transwell assay and lung metastasis were performed to analysis cell metastasis in vitro and in vivo. ECAR and OCR were used to evaluate the activity of glycolysis and mitochondrial oxidative phosphorylation. Results Our data indicated that VLCAD was downregulated in human HCC tissues and cells. VLCAD overexpression strongly suppressed the proliferation and metastasis of HCC cells associating with the decrease of ATP accumulation and glycolysis activity. Importantly, the PI3K/AKT inhibitor LY294002 strongly abolished the role of shVLCAD in HCC cells. Our results suggested that VLCAD suppressed the growth and metastasis in HCC cells by inhibiting the activities of glycolysis and mitochondrial oxidative phosphorylation metabolism via PI3K/AKT pathway. Conclusions Together, present findings not only demonstrated the protective role of and molecular network of VLCAD in HCC cells but also indicated its and potential use as a target in the therapy of HCC.

Automated summary

The expression of VLCAD is downregulated in human HCC tissues and cells. VLCAD overexpression can suppress the proliferation and metastasis of HCC cells by inhibiting the activities of glycolysis and mitochondrial oxidative phosphorylation metabolism through the PI3K/AKT pathway.