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The molecular mechanism of ginsenoside Rh2 and its octyl ester derivative on anti-angiogenesis in cancer treatment:
Qi-Rui Hu1, Xin-Yi Zhong2, Hua Feng2,3
1State Key Laboratory of Food Science and Resources, College of Food Science, Nanchang University, Nanjing East Road, Nanchang, Jiangxi, China.
Background:
The cancer treatments that target tumor associated angiogenesis (TAA) induced by vascular endothelial growth factor A (VEGFA) have become valued. Ginsenoside Rh2 has been proved to inhibit TAA through VEGFA. However, the underlying mechanisms remain unclear. Moreover, the octyl ester derivative of Rh2 (Rh2-O) exhibited better inhibitory effects than Rh2 on liver cancer in our previous researches, which indicated that Rh2-O might also exert inhibitory effects on TAA.
Purpose:
To explore the inhibitory effects of Rh2 and Rh2-O on TAA and to investigate the underlying mechanisms.
Method:
The inhibitory effects of Rh2 and Rh2-O on TAA were evaluated by conditioned medium, co-culture, and tumor-bearing mice. The network pharmacology was used to explore the possible targets, which were subsequently verified by specific agonists or inhibitors.
Results:
Rh2 and Rh2-O could efficiently inhibit TAA in a dose-dependent manner (P < 0.05). Moreover, the enhancement on phosphorylation of PI3K and STAT3 could reverse the inhibitory effects of Rh2 and Rh2-O on TAA while N-acetylcysteine could improve the effects (P < 0.05).
Conclusion:
Rh2 and Rh2-O could inhibit TAA via inhibiting the VEGFA, which was mediated by PI3K/STAT3 and PI3K/HIF-1α pathway. Meanwhile the generation of ROS could be a foe for Rh2 and Rh2-O to inhibit TAA.
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