Codonopsis pilosula polysaccharide in synergy with dacarbazine inhibits mouse melanoma by repolarizing M2-like tumor-associated macrophages into M1-like tumor-associated macrophages

Abstract

Background: The incidence and associated mortality of melanoma have increased significantly in recent years but treatment options are plagued with many undesirable side effects. Traditional Chinese herbal medicine polysaccharides are gaining increasing attention due to their potential role in the treatment of chronic diseases including tumors and the regulation of the immune system. Methods: In this study, the potential effects of Ganoderma lucidum crude polysaccharides (GLCP) and Codonopsis pilosula crude polysaccharides (CPCP) on melanoma in C57 mice were explored. In addition, the inhibition and repolarization effect of digested Codonopsis pilosula polysaccharide (dCPP) on the proliferation of tumor-associated macrophages (TAMs) with M2-like phenotype induced by IL-4 were investigated. Results: The results showed that the various polysaccharides could significantly reduce tumor volume in melanoma mice. GLCP and GLCP + CPCP could further significantly reduce the number of CD68+ macrophages in tumors and also prolong survival in melanoma mice to a certain extent. Significantly, dCPP could inhibit the proliferation of IL-4-induced M2-like TAMs, and significantly increase the mRNA expression levels of IL-1, IL-6, iNOS and TNF-a, thereby promoting the repolarization of M2-like TAMs to M1-like TAMs. Conclusion: Overall, it could be deduced that GLCP, CPCP and dCPP hold great potential as safe therapeutic options for melanoma and an immune-modulator which may require further exploration.

Keywords

• Chinese herbal medicine polysaccharides
• In vitro simulated digestion
• M2 tumor-associated macrophages (TAMs) repolarization
• Antitumor