Details

Autor(en) / Beteiligte

• Chen, Zhe
• Wang, Man
• Lv, Xiang
• Xu, Yannan
• Wang, Xionghui
• Li, Bai
• Ling, Changquan
• Du, Juan

Titel

Sanshimao formula inhibits the hypoxia-induced pro-angiogenesis of hepatocellular carcinoma cells partly through regulating MKK6/p38 signaling pathway

Ist Teil von

• Journal of pharmacy and pharmacology, 2024-04, Vol.76 (4), p.426-434

Ort / Verlag

UK: Oxford University Press

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Abstract Objectives Sanshimao (SSM) is a traditional Chinese medicine formula for advanced hepatocellular carcinoma (HCC). This study was designed to investigate the effect of SSM on HCC-induced angiogenesis and to explore the potential mechanism. Methods The endothelial cells were cultured with HCC cells conditioned medium in the 1% oxygen atmosphere to imitate tumor hypoxia microenvironment. EA.hy926 cells migration and tubulogenesis were detected by tube formation and scratch-wound assay. The protein microarray was employed to explore SSM-targeted proteins in Huh7 cells. We also established an animal model to observe the effects of SSM on angiogenesis in vivo. Results The data indicated that SSM reduced HCC-induced migration and tube formation of EA.hy926 cells at low dose under hypoxic conditions. These effects might be partly owing to suppression of HIF-1α-induced vascular endothelial growth factorα expression in Huh7 cells. Moreover, this inhibition was in an MKK6/P38-dependent way. Besides, Huh7 subcutaneous tumor models in nude mice further demonstrated the inhibition of SSM on tumor weight might be exerted partly by reduction of angiogenesis via blocking MKK6/P38 signaling pathways. Conclusion SSM inhibits HCC-induced pro-angiogenesis under hypoxic conditions via suppression of MKK6/P38 signaling pathways, which is favorable for HCC tumor growth.