Proanthocyanidin B2 inhibits proliferation and induces apoptosis of osteosarcoma cells by suppressing the PI3K/AKT pathway

J Cell Mol Med. 2020 Oct;24(20):11960-11971. doi: 10.1111/jcmm.15818. Epub 2020 Sep 10.

Abstract

Osteosarcoma (OS) is the most common primary malignant bone tumour in children and adolescents. The long-term survival rate of OS patients is stubbornly low mainly due to the chemotherapy resistance. We therefore aimed to investigate the antitumoral effects and underlying mechanisms of proanthocyanidin B2 (PB2) on OS cells in the current study. The effect of PB2 on the proliferation and apoptosis of OS cell lines was assessed by CCK-8, colony formation, and flow cytometry assays. The target gene and protein expression levels were measured by qRT-PCR and Western blotting. A xenograft mouse model was established to assess the effects of PB2 on OS proliferation and apoptosis in vivo. Results from in vitro experiments showed that PB2 inhibited the proliferation and induced apoptosis of OS cells, and also increased the expression levels of apoptosis-related proteins. Moreover, PB2 induced OS cell apoptosis through suppressing the PI3K/AKT signalling pathway. The in vivo experiments further confirmed that PB2 could inhibit OS tumour growth and induce its apoptosis. Taken together, these results suggested that PB2 inhibited the proliferation and induced apoptosis of OS cells through the suppression of the PI3K/AKT signalling pathway.

Keywords: PI3K/AKT pathway; apoptosis; osteosarcoma; proanthocyanidin B2; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondrial Membranes / drug effects
  • Mitochondrial Membranes / metabolism
  • Osteosarcoma / enzymology*
  • Osteosarcoma / pathology*
  • Permeability
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphotyrosine / metabolism
  • Proanthocyanidins / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction* / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Proanthocyanidins
  • proanthocyanidin
  • Phosphotyrosine
  • Proto-Oncogene Proteins c-akt