Huaier shows anti-cancer activities by inhibition of cell growth, migration and energy metabolism in lung cancer through PI3K/AKT/HIF-1α pathway

J Cell Mol Med. 2021 Feb;25(4):2228-2237. doi: 10.1111/jcmm.16215. Epub 2020 Dec 30.

Abstract

Huaier has been verified to have anti-cancer effects on many tumours. However, little information is available about the effects of Huaier on non-small cell lung cancer (NSCLC). We sought to probe the anti-cancer effects and related mechanisms of Huaier on lung cancer. A549 cells were pre-treated with 2, 4 and 8 mg/mL Huaier at different time points. Thereafter, cell viability was analysed by CCK-8 and the migration and invasion were detected by Scratch test and Transwell chamber migration assay. Moreover, ELISA, Western blot, shRNA transfection and RT-PCR were conducted to discover the related gene and protein expressions of energy metabolism and phosphatidylinositol 3-kinase (PI3K)/AKT/hypoxia-inducible factor 1α (HIF-1α) pathway. Furthermore, tumour xenografts were accomplished to inspect the anti-cancer effects of Huaier. Our consequences suggested that Huaier considerably repressed cell viability and migration in a dose-dependent way. In addition, Huaier statistically suppressed glycolysis, glucose transport and lactic acid (LA) accumulation. Besides, we detected that Huaier could inactivate the PI3K/AKT/HIF-1α pathway. The in vivo data confirmed that Huaier obviously decreased tumour volume and tumour growth, reduced the glycolysis, glucose transport and HIF-1α expression in the tumour-bearing tissues. Our results suggested Huaier revealed anti-tumour effects in both in vivo and in vitro possibly through PI3K/AKT/HIF-1α pathway.

Keywords: AKT; HIF-1α pathway; Huaier; NSCLC; PI3K; energy metabolism.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Complex Mixtures / pharmacology*
  • Disease Models, Animal
  • Energy Metabolism / drug effects*
  • Glucose / metabolism
  • Glycolysis / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Lung Neoplasms
  • Male
  • Mice
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction / drug effects*
  • Trametes
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Complex Mixtures
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • huaier
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • Glucose