Angelica Sinensis Polysaccharides Ameliorate 5-Flourouracil-Induced Bone Marrow Stromal Cell Proliferation Inhibition Via Regulating Wnt/ β-Catenin Signaling

Abstract

Background: Chemotherapy-induced bone marrow hematopoietic microenvironment oxidative damage is closely related to myelosuppression. Angelica Sinensis Polysaccharides (ASP) are major effective ingredients of traditional Chinese medicine Angelica with multi-target anti-oxidative stress features. In this study, we investigated the potential benefits and mechanism of action of ASP on chemotherapy-induced bone marrow stromal cell (BMSC) damage.Methods: The human bone marrow stromal cell line HS-5 cells were divided into control group, 5-FU group, 5-FU + ASP group, and 5-FU+ LiCl group to investigate the mechanism of ASP to alleviate 5-FU-induced BMSC proliferation inhibition.Results: The results showed that 5-FU inhibits the growth of HS-5 cells in a time and dose-dependent manner; however, ASP partially counteracted 5-FU-induced decrease in cell viability, whereas Wnt signaling inhibitor Dkk1 antagonized the effect of ASP on HS-5 cells. ASP reversed the decrease in cytoplasmic total β-catenin, p-GSK-3β, and CyclinD1 following 5-FU treatment, and modulated nuclear expression of β-catenin, Lef-1, and C-myc proteins. Furthermore, ASP also enhanced the antioxidant capacity of cells and reduced 5-FU caused oxidative stress, attenuated FoxO1 expression, thus weakened its downstream apoptosis-related proteins and G0/G1 checkpoint-associated p27Kip1expression to alleviate 5-FU-induced apoptosis promote cell cycle progression. Conclusion: The protective role of ASP in BMSCs proliferation for the chemotherapy may be related to its activating Wnt/β-catenin signaling and keeping homeostasis between β-catenin and FoxO1 under oxidative stress. The study provides a potential therapeutic strategy for alleviating chemotherapeutic damage on BMSCs.