Baohuoside I Inhibits Tumor Angiogenesis in Multiple Myeloma via the Peroxisome Proliferator-Activated Receptor γ/Vascular Endothelial Growth Factor Signaling Pathway

Angiogenesis plays an important role in the development of multiple myeloma (MM). Baohuoside I (BI) is a core flavonoid monomer with anticancer property. However, the mechanism of BI on MM-stimulated angiogenesis has not been revealed. In this study, we demonstrated that BI inhibits MM-induced angiogenesis in vitro and angiogenesis in a xenograft mouse model in vivo. We further showed that peroxisome proliferator-activated receptor gamma (PPAR gamma) transcriptional activity was mediated by a direct physical association between BI and PPAR gamma. Meanwhile, inhibition of PPAR gamma using lentivirus transfection of shRNA in human myeloma cell lines showed that the facilitation of PPAR gamma blocked angiogenesis and PPAR gamma repressed vascular endothelial growth factor (VEGF) transcription. Furthermore, BI treatment decreased VEGF expression, whereas VEGF expression remained unchanged after PPAR gamma knockdown when exposed to BI. Overall, our study is the first to reveal that BI inhibits MM angiogenesis by the PPAR gamma-VEGF signaling axis.

Automated summary

This study reveals for the first time that Baohuoside I (BI) inhibits angiogenesis in multiple myeloma (MM) through the PPARγ-VEGF signaling axis.