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. 2021 Feb 10;12:618773. doi: 10.3389/fphar.2021.618773

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Copyright © 2021 Choi, Mohamad Zobir, Alexander-Dann, Sharma, Ma, Lam, Yeo, Zhang, Fan and Bender.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Effects of selective inhibitors of Akt ((A); LY294002), CXCR1/2 ((B); Reparixin) and ERK ((C); U0126) on Rb2/Rg3-induced cell proliferation as monitored by the CCK-8 assay, indicating the pro-proliferative effects of the combination were due to activation of at least those three pathways. The effect of the CXCR1/2 inhibitor was most profound and entirely inhibited the stimulation of cell proliferation due to ginsenoside treatment. Data represents mean ± SD, n = 4. **p < 0.005 and ###p < 0.001. (D) Phosphorylation of Akt and ERK by the combination of Rb2 and Rg3 in the presence or absence of LY294002 and U0126 as measured by western blotting and the density of bands were measured. LY294002 and U0126 completely inhibited the promoting effects of Rb2 and Rg3 on the phosphorylation of Akt and ERK, respectively. These results demonstrate that Akt and ERK, and their phosphorylation, are essential for the pro-proliferative effects of the Rb2/Rg3 combination.