Saikosaponin A, a Triterpene Saponin, Suppresses Angiogenesis and Tumor Growth by Blocking VEGFR2-Mediated Signaling Pathway

Pan Zhang; Xing Lai; Mao-Hua Zhu; Mei Long; Xue-Liang Liu; Zi-Xiang Wang; Yifan Zhang; Run-Jie Guo; Jing Dong; Qin Lu; Peng Sun; Chao Fang; Mei Zhao

doi:10.3389/fphar.2021.713200

Saikosaponin A, a Triterpene Saponin, Suppresses Angiogenesis and Tumor Growth by Blocking VEGFR2-Mediated Signaling Pathway

Front Pharmacol. 2021 Oct 29:12:713200. doi: 10.3389/fphar.2021.713200. eCollection 2021.

Authors

Pan Zhang^{1

2}, Xing Lai³, Mao-Hua Zhu³, Mei Long³, Xue-Liang Liu³, Zi-Xiang Wang¹, Yifan Zhang¹, Run-Jie Guo², Jing Dong³, Qin Lu³, Peng Sun⁴, Chao Fang³, Mei Zhao^{1

2}

Affiliations

¹ Department of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai, China.
² Graduate School, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
³ Tongren Hospital and State Key Laboratory of Oncogenes and Related Genes, Department of Pharmacology and Chemical Biology, Hongqiao International Institute of Medicine, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China.
⁴ Department of General Surgery, Tongren Hospital, SJTU-SM, Shanghai, China.

Abstract

Saikosaponin A (SSA), a main triterpenoid saponin component from Radix Bupleurum, has been revealed to have a variety of pharmacological activities. However, whether SSA can inhibit angiogenesis, a key step in solid tumor progression, remains unknown. In this study, we demonstrated that SSA could powerfully suppress the proliferation, migration, and tube formation of human umbilical vein endothelial cells. SSA also significantly inhibited angiogenesis in the models of the chick embryo chorioallantoic membrane and Matrigel plugs. Moreover, SSA was found to inhibit tumor growth in both orthotopic 4T1 breast cancer and subcutaneous HCT-15 colorectal tumor by the inhibition of tumor angiogenesis. Western blot assay indicated the antiangiogenic mechanism of SSA in the suppression of the protein phosphorylation of VEGFR2 and the downstream protein kinase including PLCγ1, FAK, Src, and Akt. In summary, SSA can suppress angiogenesis and tumor growth by blocking the VEGFR2-mediated signaling pathway.

Keywords: VEGFR2; angiogenesis; cancer therapy; chick embryo chorioallantoic membrane; saikosaponin A.