Geniposide inhibits non-small cell lung cancer cell migration and angiogenesis by regulating PPARγ/VEGF-A pathway

Abstract

Geniposide, an iridoid glycoside derived from traditional Chinese herb, Gardenia jasminoides Ellis, exerts antitumor effect against distinct cancers. The role of geniposide in the migration and angiogenesis of non-small cell lung cancer (NSCLC) cell was investigated in this study. Cancer cells were incubated with various concentrations of geniposide, and proliferative ability was detected by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) staining. Wound healing and transwell were used to assess cell migration and invasion, respectively. Tube formation assay was performed to investigate angiogenesis. Geniposide reduced NSCLC cell proliferation, and suppressed NSCLC cell migration and invasion in a dosage-dependent manner. Angiogenesis of NSCLC was also inhibited by geniposide. Geniposide increased the protein expression of peroxisome proliferator-activated receptor gamma (PPARγ) and decreased vascular endothelial growth factor-A (VEGF-A) protein expression in NSCLC cells. Incubation with a PPARγ antagonist, GW9662, attenuated geniposide-induced up-regulation of PPARγ and down-regulation of VEGF-A. Over-expression of VEGF-A weakened geniposide-suppressed cell proliferation, migration, and angiogenesis of NSCLC. Geniposide exerted antitumor and anti-angiogenic actions on NSCLC through regulation of PPARγ/VEGF-A pathway.