Abiraterone suppresses irradiated lung cancer cells-induced angiogenic capacities of endothelial cells

J Bioenerg Biomembr. 2021 Jun;53(3):343-349. doi: 10.1007/s10863-021-09894-4. Epub 2021 Apr 5.

Abstract

Non-small cell lung cancer (NSCLC) threatens human life globally with high morbidity and mortality and radiotherapy is one of the most effective methods for the treatment of NSCLC. However, it is currently reported that the angiogenesis of tumors can be induced by a low dosage of irradiation. Abiraterone is an oral anti-tumor agent for the treatment of castration-resistant prostate cancer (CRPC). In the present study, the anti-angiogenesis effect of Abiraterone against HUVECs incubated with irradiated lung cancer cell medium will be investigated. The HUVECs were incubated with a cultural medium of the NSCLC cell line-A549, Abiraterone-treated A549 cells, irradiation-treated A549 cells, and Abiraterone and irradiation co-treated A549 cells. The tolerable concentration of Abiraterone against HUVECs was determined using MTT assay. The migration and angiogenesis abilities of HUVECs were evaluated using transwell and tube formation assays, respectively. The expression levels of VEGF, MMP-2, and MMP-9 in the treated HUVECs were detected using qRT-PCR and ELISA. Western blot was used to determine the expressions of p-PI3K and p-AKT. The tolerable concentration of Abiraterone used in the present study was 50 nM. First, the migration rate and numbers of formed tubes were significantly decreased by the A549 medium treated with Abiraterone and elevated by the A549 medium treated with irradiation but greatly suppressed by the co-treatment with Abiraterone. Subsequently, VEGF, MMP-2, and MMP-9 were significantly downregulated by the A549 medium treated with Abiraterone and upregulated by the A549 medium treated with irradiation but greatly inhibited by the co-treatment with Abiraterone. Lastly, the activated PI3K/AKT signaling pathway induced by the A549 medium treated with irradiation was significantly suppressed by the A549 medium treated with both irradiation and Abiraterone. Abiraterone suppressed irradiated lung cancer cells-induced angiogenic capacities of endothelial cells.

Keywords: Abiraterone; Angiogenesis; Irradiation; NSCLC; VEGF.

MeSH terms

  • Androstenes / pharmacology
  • Androstenes / therapeutic use*
  • Endothelial Cells
  • Humans
  • Lung Neoplasms / drug therapy*

Substances

  • Androstenes
  • abiraterone