AUTHOR=Bao Wan-Rong , Li Zhi-Peng , Zhang Quan-Wei , Li Li-Feng , Liu Hong-Bing , Ma Dik-Lung , Leung Chung-Hang , Lu Ai-Ping , Bian Zhao-Xiang , Han Quan-Bin 

TITLE=Astragalus Polysaccharide RAP Selectively Attenuates Paclitaxel-Induced Cytotoxicity Toward RAW 264.7 Cells by Reversing Cell Cycle Arrest and Apoptosis

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.01580

DOI=10.3389/fphar.2018.01580

ISSN=1663-9812

ABSTRACT=<p><bold>Purpose:</bold> The purpose of this study was to determine if an <italic>Astragalus</italic> polysaccharide (RAP) can protect immune cells from the toxic side effects of paclitaxel (Taxol), a powerful anti-tumor drug whose equally powerful side effects limit its clinical use.</p><p><bold>Methods:</bold> We hypothesized that RAP can reduce the toxic effects induced by Taxol. To test this hypothesis, we conducted a series of studies <italic>in vivo</italic> and <italic>in vitro</italic>. First, we confirmed RAP’s effects <italic>in vivo</italic> utilizing BALB/c mice inoculated with 4T1 mouse breast cancer cells as the tumor model. Mice were treated with RAP and/or Taxol, and the differences in the life spans were recorded. Second, a co-culture cell model was used to study the protective effect of RAP on cells vis-a-vis Taxol. The cell cycle and apoptosis of RAW 264.7 cells that were treated with RAP with/without Taxol were checked by flow cytometry and Hoechst staining. Proteins involved in the cell cycle and apoptosis were also tested by Western blot to reveal the probable mechanism.</p><p><bold>Results:</bold> RAP prolonged the life span of tumor-bearing mice treated with Taxol. The <italic>in vitro</italic> experiments showed that Taxol suppressed the proliferation of RAW 264.7 cells while RAP protected the RAW 264.7 cells from Taxol-induced suppression. The protection is selective because RAP had no effect on 4T1 cells. Furthermore, Taxol clearly led to cell cycle arrest mainly at the G2/M phase and generated cytotoxicity against RAW 264.7 cells, while RAP blocked cell cycle arrest and protected cells from apoptosis. Taxol up-regulated the protein levels of P-H<sub>2</sub>A, PARP, Chk1, p53, and p21 and down-regulated Bcl-Xl and Mcl-1, and RAP reversed the expression of all these proteins.</p><p><bold>Conclusion:</bold> These results suggested that RAP can protect immune cells from Taxol-induced toxicity, by changing the cell cycle and apoptosis.</p>