2. Academic Validation
  3. To explore the potential combined treatment strategy for colorectal cancer: Inhibition of cancer stem cells and enhancement of intestinal immune microenvironment

To explore the potential combined treatment strategy for colorectal cancer: Inhibition of cancer stem cells and enhancement of intestinal immune microenvironment

  • Eur J Pharmacol. 2025 Mar 20:998:177533. doi: 10.1016/j.ejphar.2025.177533.
Dan-Qi Xu 1,  Jia-Xin Geng 1,  Zhan-Kui Gao 1,  Chao-Yuan Fan 1,  Bo-Wen Zhang 1,  Xing Han 1,  Li-Qian He 1,  Lin Dai 1,  Shuo Gao 1,  Zhou Yang 1,  Yang Zhang 1,  Muhammad Arshad 1,  Yin Fu 2,  Xiao-Qin Mu 3
Affiliations

Affiliations

  • 1 Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province), College of Pharmacy, Harbin Medical University, Harbin, 150081, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin Medical University, Harbin, 150081, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, 150081, China; HMU-UCCSM Centre for Infection and Genomics, Harbin Medical University, Harbin, 150081, China.
  • 2 School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, 150006, China. Electronic address: fuyin0921@163.com.
  • 3 Genomics Research Center (Key Laboratory of Gut Microbiota and Pharmacogenomics of Heilongjiang Province), College of Pharmacy, Harbin Medical University, Harbin, 150081, China; National Key Laboratory of Frigid Zone Cardiovascular Diseases, Harbin Medical University, Harbin, 150081, China; Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, 150081, China; HMU-UCCSM Centre for Infection and Genomics, Harbin Medical University, Harbin, 150081, China. Electronic address: muxiaoqin@ems.hrbmu.edu.cn.
PMID: 40120791 DOI: 10.1016/j.ejphar.2025.177533
Abstract

Background: The Antibiotic salinomycin, a well-known Cancer stem cell inhibitor, may impact the diversity of the intestinal microbiota in colorectal Cancer (CRC) mice, which plays a pivotal role in shaping the immune system. This study explores the anti-cancer effects and mechanisms of combining salinomycin and fecal microbiota transplantation (FMT) in treating CRC.

Methods: FMT was given via enema, while salinomycin was injected intraperitoneally into the CRC mouse model induced by azoxymethane/dextran sodium sulfate.

Results: In CRC mice, a large number of LGR5-labeled Cancer Stem Cells and severe disturbances in the intestinal microbiota were observed. Interestingly, salinomycin inhibited the proliferation of Cancer Stem Cells without exacerbating the microbial disorder as expected. In comparison to salinomycin treatment, the combination of salinomycin and FMT significantly improved pathological damage and restored intestinal microbial diversity, which is responsible for shaping the anti-cancer immune microenvironment. The supplementation of FMT significantly increased the levels of propionic acid and butyric acid while also promoting the infiltration of CD8+ T cells and Ly6G+ neutrophils, as well as reducing F4/80+ macrophage recruitment. Notably, cytokines that were not impacted by salinomycin exhibited robust reactions to alterations in the gut microbiota. These included pro-inflammatory factors (IL6, IL12b, IL17, and IL22), chemokine-like protein OPN, and immunosuppressive factor PD-L1.

Conclusions: Salinomycin plays the role of "eliminating pathogenic qi," targeting Cancer stem cells; FMT plays the role of "strengthening vital qi," reversing the intestinal microbiota disorder and enhancing anti-cancer immunity. They have a synergistic effect on the development of CRC.

Keywords

Cancer stem cells; Colorectal cancer; Fecal microbiota transplantation; Immune microenvironment; Salinomycin.

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