Atractylodes macrocephala polysaccharides regulate the innate immunity of colorectal cancer cells by modulating the TLR4 signaling pathway

BACKGROUND: It has been well-recognized that the polysaccharides from Atractylodes macrocephala (PAM) are immune system enhancers, which can facilitate the proliferation of lymphocytes and stimulate immune cells. Nevertheless, the antitumor effects of PAM and their molecular mechanisms remain unclear. AIM: Our research aimed to evaluate the anti-cancer effects of PAM on colorectal cancer (CRC). METHODS: We tested the effects of PAM on the growth and proliferation of CRC cells and macrophages by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The pro-inflammatory cytokines expression and secretion was analyzed by real-time RT-PCR and ELISA assay. We also used MC38 cells xenograft model to test the anti-cancer effects of PAM in vivo. RESULTS: We found that although PAM treatment did not significantly affect the growth of CRC cells or enhance the proliferation of bone marrow-derived macrophages (BMDMs), it could enhance the phagocytosis of BMDMs by CRC cells. Biochemical tests and immunoblotting assays revealed that exposing BMDMs to PAM promoted the production of interleukin-6 (IL-6), interferon λ (IFN λ), tumor necrosis factor α (TNF-α), and nitric oxide (NO) through the MyD88/TLR4-dependent signaling pathway. One noteworthy observation is that PAM treatment could significantly prevent tumorigenesis of MC38 cells in C57BL/6J mice and increase the survival duration of mice with tumors, without influence on the weight of those mice. However, the anti-cancer effects of PAM were compromised in TLR4 KO mice, further suggesting that TLR4 signaling plays a vital role in the anti-cancer effects of PAM. CONCLUSION: Therefore, PAM may prove to be a potential candidate in cancer immunotherapy.