PMID- 31564895 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220410 IS - 1178-6930 (Print) IS - 1178-6930 (Electronic) IS - 1178-6930 (Linking) VI - 12 DP - 2019 TI - Atractylodes macrocephala polysaccharides regulate the innate immunity of colorectal cancer cells by modulating the TLR4 signaling pathway. PG - 7111-7121 LID - 10.2147/OTT.S219623 [doi] AB - 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 lambda (IFN lambda), tumor necrosis factor alpha (TNF-alpha), 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. CI - (c) 2019 Feng et al. FAU - Feng, Zifang AU - Feng Z AD - Department of Laboratory, Xingyi City People's Hospital, Xingyi, People's Republic of China. FAU - Yang, Ruibin AU - Yang R AD - Department of Laboratory, Xingyi City People's Hospital, Xingyi, People's Republic of China. FAU - Wu, Liusong AU - Wu L AD - Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, People's Republic of China. FAU - Tang, Shihua AU - Tang S AD - Department of Laboratory, Xingyi City People's Hospital, Xingyi, People's Republic of China. FAU - Wei, Bin AU - Wei B AD - Department of Laboratory, Xingyi City People's Hospital, Xingyi, People's Republic of China. FAU - Guo, Lijia AU - Guo L AD - Department of Laboratory, Xingyi City People's Hospital, Xingyi, People's Republic of China. FAU - He, Ling AU - He L AD - Department of Laboratory, Xingyi City People's Hospital, Xingyi, People's Republic of China. FAU - Feng, Yonghuai AU - Feng Y AD - Department of Haematology, Affiliated Hospital of Zunyi Medical University, Zunyi, People's Republic of China. LA - eng PT - Journal Article DEP - 20190904 PL - New Zealand TA - Onco Targets Ther JT - OncoTargets and therapy JID - 101514322 PMC - PMC6733773 OTO - NOTNLM OT - TLR4 OT - cancer immunotherapy OT - colorectal cancer OT - macrophages OT - polysaccharides from Atractylodes macrocephala COIS- The authors declare that there are no conflicts of interest in this work. EDAT- 2019/10/01 06:00 MHDA- 2019/10/01 06:01 PMCR- 2019/09/04 CRDT- 2019/10/01 06:00 PHST- 2019/06/15 00:00 [received] PHST- 2019/08/01 00:00 [accepted] PHST- 2019/10/01 06:00 [entrez] PHST- 2019/10/01 06:00 [pubmed] PHST- 2019/10/01 06:01 [medline] PHST- 2019/09/04 00:00 [pmc-release] AID - 219623 [pii] AID - 10.2147/OTT.S219623 [doi] PST - epublish SO - Onco Targets Ther. 2019 Sep 4;12:7111-7121. doi: 10.2147/OTT.S219623. eCollection 2019.