2. Academic Validation
  3. Fucoidan, as an immunostimulator promotes M1 macrophage differentiation and enhances the chemotherapeutic sensitivity of capecitabine in colon cancer

Fucoidan, as an immunostimulator promotes M1 macrophage differentiation and enhances the chemotherapeutic sensitivity of capecitabine in colon cancer

  • Int J Biol Macromol. 2022 Sep 25;222(Pt A):562-572. doi: 10.1016/j.ijbiomac.2022.09.201.
Zhenzhen Deng 1,  Ning Wu 2,  Qishan Suo 1,  Jing Wang 3,  Yang Yue 3,  Lihua Geng 3,  Quanbin Zhang 4
Affiliations

Affiliations

  • 1 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Lab for Marine Biology and Biotechnology, Qingdao National Lab for Marine Sci. & Tech, Qingdao 266071, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine drugs and biological products, Pilot National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address: wuning@qdio.ac.cn.
  • 3 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Lab for Marine Biology and Biotechnology, Qingdao National Lab for Marine Sci. & Tech, Qingdao 266071, China.
  • 4 CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Lab for Marine Biology and Biotechnology, Qingdao National Lab for Marine Sci. & Tech, Qingdao 266071, China. Electronic address: qbzhang@qdio.ac.cn.
PMID: 36170928 DOI: 10.1016/j.ijbiomac.2022.09.201
Abstract

Chemotherapy resistance is one of the most critical challenges in colorectal Cancer (CRC) treatment. The occurrence and development of chemotherapy resistance closely related to the tumor immune microenvironment (TIME). As the most important immunosuppressive immune cells infiltrating into the TIME, macrophages are essential for chemotherapy resistance in CRC treatment. In this study, we found that a kind of fucoidan (FPS1M) induced macrophages differentiation to the M1 phenotype, and this transformation promoted Cancer cells Apoptosis both in vitro and in vivo. TNFα is a key mediator of FPS1M-induced tumorcidal activity of macrophages. Mechanistically, as a stimulator of TLR4, FPS1M enhanced macrophages glycolysis and regulated macrophages differentiation to the M1 phenotype by the activation of TLR4 mediated PI3K/Akt/mTOR signaling axis. In addition, FPS1M improved the immunosuppressed tumor microenvironment by increasing the infiltration of M1 macrophages in tumor tissue, which was conducive to improving the sensitivity of tumor to chemotherapy. Collectively, our findings demonstrated that FPS1M has the great potential to be used in tumor immunotherapy. The results also suggested that the combination of FPS1M with capecitabine is an alternative therapy method for colon Cancer.

Keywords

Capecitabine; Fucoidan; Macrophages; TLR4; Tumor microenvironment.

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