2. Academic Validation
  3. Dioscin modulates macrophages polarization and MDSCs differentiation to inhibit tumorigenesis of colitis-associated colorectal cancer

Dioscin modulates macrophages polarization and MDSCs differentiation to inhibit tumorigenesis of colitis-associated colorectal cancer

  • Int Immunopharmacol. 2023 Feb 19;117:109839. doi: 10.1016/j.intimp.2023.109839.
Jing Xun 1,  Siying Zhou 2,  Zongjing Lv 2,  Botao Wang 3,  Hai Luo 2,  Lanqiu Zhang 1,  Lei Yang 1,  Aimin Zhang 4,  Xueliang Wu 5,  Zhenyu Wang 1,  Ximo Wang 6,  Xiangyang Yu 7,  Qi Zhang 8
Affiliations

Affiliations

  • 1 Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China.
  • 2 Graduate School, Tianjin Medical University, Tianjin 300100, China.
  • 3 Chongqing Traditional Chinese Medicine Hospital, Chongqing 400021, China.
  • 4 Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China.
  • 5 Department of General Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou 075000, China.
  • 6 Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China; Institute of Integrative Medicine for Acute Abdominal Diseases, Tianjin Medical University, Tianjin 300100, China.
  • 7 Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China. Electronic address: yxynankai@126.com.
  • 8 Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China; Integrated Chinese and Western Medicine Hospital, Tianjin University, Tianjin 300100, China. Electronic address: zhangqi8501@126.com.
PMID: 36809720 DOI: 10.1016/j.intimp.2023.109839
Abstract

It has been reported that colitis is one of risk factors in colorectal Cancer (CRC). Intervention of intestinal inflammation and in the early stage of tumorigenesis is of great significance to control the incidence and mortality of CRC. In recent years, natural active products of traditional Chinese medicine have been confirmed that they had made great progress in disease prevention. Here, we showed that Dioscin, a natural active product of Dioscorea nipponica Makino, inhibited initiation and tumorigenesis of AOM/DSS-induced colitis-associated colon Cancer (CAC), including alleviating colonic inflammation, improving intestinal barrier function and decreasing tumor burden. In addition, we also explored the immunoregulatory effect of Dioscin on mice. The results showed that Dioscin modulated M1/M2 macrophages phenotype in spleen and decreased monocytic myeloid-derived suppressor cells (M-MDSCs) population in blood and spleen of mice. The in vitro assay demonstrated that Dioscin promoted M1 as well as inhibited M2 macrophages phenotype in LPS- or IL-4-induced bone marrow-derived macrophages (BMDMs) model. Based on the plasticity of MDSCs and its ability to differentiate into M1/M2 macrophages, we here found that Dioscin increased M1- and decreased M2-like phenotype during the process of MDSCs differentiation in vitro, suggesting Dioscin promoted MDSCs differentiate into M1 as well as inhibited its differentiation into M2 macrophages. Taken together, our study indicated that Dioscin had the inhibitory effect on the initial of tumorigenesis at early stage of CAC via the ant-inflammatory effect, which provided a natural active candidate for effective prevention of CAC.

Keywords

Colitis-associated colorectal cancer; Dioscin; Macrophage polarization; Myeloid-derived suppressor cells; Tumorigenesis.

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