Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing -induced Aerobic Glycolysis
Aim: Quxie capsule (QX), a compound of 21 kinds of Traditional Chinese Medicine (TCM) herbs, has been used to treat patients with metastatic colorectal cancer (mCRC) and could suppress the growth of colon cancer. However, the mechanisms of QX inhibiting colorectal cancer remain unclear. In current s...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2022-11-01
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| Series: | Integrative Cancer Therapies |
| Online Access: | https://doi.org/10.1177/15347354221138534 |
| _version_ | 1811179556724277248 |
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| author | Zhiyong Zhang Yuxi Chen Yaojun Zheng Lei Wang Sunan Shen Geliang Yang Yufei Yang Tingting Wang |
| author_facet | Zhiyong Zhang Yuxi Chen Yaojun Zheng Lei Wang Sunan Shen Geliang Yang Yufei Yang Tingting Wang |
| author_sort | Zhiyong Zhang |
| collection | DOAJ |
| description | Aim: Quxie capsule (QX), a compound of 21 kinds of Traditional Chinese Medicine (TCM) herbs, has been used to treat patients with metastatic colorectal cancer (mCRC) and could suppress the growth of colon cancer. However, the mechanisms of QX inhibiting colorectal cancer remain unclear. In current study, we attempted to determine the anti-colorectal cancer (CRC) effects of QX and the mechanisms of QX in alleviating colorectal cancer. Methods: A colitis-associated colon cancer (CAC) model was established by intraperitoneally injecting mice with AOM followed by 3 cycles of 2% DSS in water. During establishment of CAC model, we orally gavaged mice with QX. Hematoxylin and eosin (H&E) and immunohistochemistry were performed to assess lesion of the colonic tumors. The expression of pro-inflammatory cytokines in colonic tumors was measured by qPCR. The proportion of immune cells in colonic tumors was analyzed by flow cytometry. Internal transcribed spacer (ITS) sequencing and 16S rRNA gene sequencing were performed to detect intestinal microbiota. The expression of glycolytic related enzymes, lactate production, and extracellular acidification rate (ECAR) were used to assess the level of aerobic glycolysis. Results: QX markedly inhibited intestinal tumorigenesis by decreasing the expression of pro-inflammatory cytokines and the proportion of myeloid-derived suppressor cells (MDSCs), and increasing the proportion of CD8 + T cells in colon tumors. Fecal microbiota sequencing revealed that QX increased the relative abundances of intestinal symbiotic probiotics, such as, Lactobacillus , Bifidobacterium and Faecalibacterium genera. What’s more, opportunistic pathogens, Bacteroides genera and Aspergillus - Aspergillus fumigatus , exhibited remarkably reduced abundances in mice treated with QX compared with untreated CAC mice. Further experiments showed that QX significantly reduced glycolysis of colon tumor and suppressed A. fumigatus -induced glycolytic metabolism of colon cancer cells. Conclusions: QX alleviates the development of CRC at least in part through modulating intestinal microbiota and reducing A. fumigatus -induced aerobic glycolysis of colon cancer cells. |
| first_indexed | 2024-04-11T06:36:19Z |
| format | Article |
| id | doaj.art-8a601245c17e4ea3b0131b3f3952b663 |
| institution | Directory Open Access Journal |
| issn | 1552-695X |
| language | English |
| last_indexed | 2024-04-11T06:36:19Z |
| publishDate | 2022-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Integrative Cancer Therapies |
| spelling | doaj.art-8a601245c17e4ea3b0131b3f3952b6632022-12-22T04:39:42ZengSAGE PublishingIntegrative Cancer Therapies1552-695X2022-11-012110.1177/15347354221138534Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing -induced Aerobic GlycolysisZhiyong Zhang0Yuxi Chen1Yaojun Zheng2Lei Wang3Sunan Shen4Geliang Yang5Yufei Yang6Tingting Wang7Jiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing, ChinaJiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing, ChinaJiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing, ChinaClinical Cancer Center of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaJiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing, ChinaDepartment of Medicine, Shanghai Clinical Research Center, Shanghai, ChinaClinical Cancer Center of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, ChinaJiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing, ChinaAim: Quxie capsule (QX), a compound of 21 kinds of Traditional Chinese Medicine (TCM) herbs, has been used to treat patients with metastatic colorectal cancer (mCRC) and could suppress the growth of colon cancer. However, the mechanisms of QX inhibiting colorectal cancer remain unclear. In current study, we attempted to determine the anti-colorectal cancer (CRC) effects of QX and the mechanisms of QX in alleviating colorectal cancer. Methods: A colitis-associated colon cancer (CAC) model was established by intraperitoneally injecting mice with AOM followed by 3 cycles of 2% DSS in water. During establishment of CAC model, we orally gavaged mice with QX. Hematoxylin and eosin (H&E) and immunohistochemistry were performed to assess lesion of the colonic tumors. The expression of pro-inflammatory cytokines in colonic tumors was measured by qPCR. The proportion of immune cells in colonic tumors was analyzed by flow cytometry. Internal transcribed spacer (ITS) sequencing and 16S rRNA gene sequencing were performed to detect intestinal microbiota. The expression of glycolytic related enzymes, lactate production, and extracellular acidification rate (ECAR) were used to assess the level of aerobic glycolysis. Results: QX markedly inhibited intestinal tumorigenesis by decreasing the expression of pro-inflammatory cytokines and the proportion of myeloid-derived suppressor cells (MDSCs), and increasing the proportion of CD8 + T cells in colon tumors. Fecal microbiota sequencing revealed that QX increased the relative abundances of intestinal symbiotic probiotics, such as, Lactobacillus , Bifidobacterium and Faecalibacterium genera. What’s more, opportunistic pathogens, Bacteroides genera and Aspergillus - Aspergillus fumigatus , exhibited remarkably reduced abundances in mice treated with QX compared with untreated CAC mice. Further experiments showed that QX significantly reduced glycolysis of colon tumor and suppressed A. fumigatus -induced glycolytic metabolism of colon cancer cells. Conclusions: QX alleviates the development of CRC at least in part through modulating intestinal microbiota and reducing A. fumigatus -induced aerobic glycolysis of colon cancer cells.https://doi.org/10.1177/15347354221138534 |
| spellingShingle | Zhiyong Zhang Yuxi Chen Yaojun Zheng Lei Wang Sunan Shen Geliang Yang Yufei Yang Tingting Wang Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing -induced Aerobic Glycolysis Integrative Cancer Therapies |
| title | Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing -induced Aerobic Glycolysis |
| title_full | Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing -induced Aerobic Glycolysis |
| title_fullStr | Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing -induced Aerobic Glycolysis |
| title_full_unstemmed | Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing -induced Aerobic Glycolysis |
| title_short | Quxie Capsule Alleviates Colitis-associated Colorectal Cancer Through Modulating the Gut Microbiota and Suppressing -induced Aerobic Glycolysis |
| title_sort | quxie capsule alleviates colitis associated colorectal cancer through modulating the gut microbiota and suppressing induced aerobic glycolysis |
| url | https://doi.org/10.1177/15347354221138534 |
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