https://scholars.lib.ntu.edu.tw/handle/123456789/635346
標題: | The protective effect of cannabinoids against colorectal cancer cachexia through modulation of inflammation and immune responses | 作者: | Ng, Shang-Kok Chung, Dai-Jung LI-CHUN CHANG Luo, Cong-Kai Jwo, Si-Han Lee, Yau-Hsuan JR-SHIUAN LIN Wang, Chun-Hao TZU-TANG WEI |
關鍵字: | CD8(+) T cell; Cannabinoid receptor 2; Cannabinoids; Colorectal cancer cachexia; Cytokines | 公開日期: | 五月-2023 | 出版社: | Elsevier Masson s.r.l. | 卷: | 161 | 起(迄)頁: | 114467 | 來源出版物: | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | 摘要: | Cancer cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, and there are currently no FDA-approved medications. In the present study, upregulation of six cytokines was observed in serum samples from patients with colorectal cancer (CRC) and in mouse models. A negative correlation between the levels of the six cytokines and body mass index in CRC patients was seen. Gene Ontology analysis revealed that these cytokines were involved in regulating T cell proliferation. The infiltration of CD8+ T cells was found to be associated with muscle atrophy in mice with CRC. Adoptive transfer of CD8+ T cells isolated from CRC mice resulted in muscle wasting in recipients. The Genotype-Tissue Expression database showed that negative correlations between the expression of cachexia markers and cannabinoid receptor 2 (CB2) in human skeletal muscle tissues. Pharmacological treatment with Δ9-tetrahydrocannabinol (Δ9-THC), a selective CB2 agonist or overexpression of CB2 attenuated CRC-associated muscle atrophy. In contrast, knockout of CB2 with a CRISPR/Cas9-based strategy or depletion of CD8+ T cells in CRC mice abolished the Δ9-THC-mediated effects. This study demonstrates that cannabinoids ameliorate CD8+ T cell infiltration in CRC-associated skeletal muscle atrophy via a CB2-mediated pathway. Serum levels of the six-cytokine signature might serve as a potential biomarker to detect the therapeutic effects of cannabinoids in CRC-associated cachexia. |
URI: | https://www.scopus.com/record/display.uri?eid=2-s2.0-85149396576&doi=10.1016%2fj.biopha.2023.114467&origin=inward&txGid=0f37f72bd9455c38a1ff91ccbc8ec8ae https://scholars.lib.ntu.edu.tw/handle/123456789/635346 |
ISSN: | 0753-3322 | DOI: | 10.1016/j.biopha.2023.114467 |
顯示於: | 醫學系 |
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