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

• QW Zhu ^[2] ; Yue Yu ^[3] ; Yu Zhang ^[1] ; XH Wang ^[4]
  1. [1] Nanjing Medical University

     Nanjing Medical University

     China

     
  2. [2] Department of General Surgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, China
  3. [3] Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China
  4. [4] Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China

  Mostrar afiliaciones +
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 24, Nº. 5 (May), 2022, págs. 864-874
• Idioma: inglés
• Enlaces
  • Texto completo (pdf)
• Resumen

  • 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.