دورية أكاديمية
Blocking Muscarinic Receptor 3 Attenuates Tumor Growth and Decreases Immunosuppressive and Cholinergic Markers in an Orthotopic Mouse Model of Colorectal Cancer
| العنوان: | Blocking Muscarinic Receptor 3 Attenuates Tumor Growth and Decreases Immunosuppressive and Cholinergic Markers in an Orthotopic Mouse Model of Colorectal Cancer |
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| المؤلفون: | Nyanbol Kuol, Majid Davidson, Jimsheena Karakkat, Rhiannon T. Filippone, Margaret Veale, Rodney Luwor, Sarah Fraser, Vasso Apostolopoulos, Kulmira Nurgali |
| المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 1, p 596 (2022) |
| بيانات النشر: | MDPI AG, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Chemistry |
| مصطلحات موضوعية: | colorectal cancer, immunosuppressive, programmed death ligands 1 and 2, muscarinic receptor 3, α7 nicotinic acetylcholine receptor, choline acetyltransferase, Biology (General), QH301-705.5, Chemistry, QD1-999 |
| الوصف: | Tumor cells have evolved to express immunosuppressive molecules allowing their evasion from the host’s immune system. These molecules include programmed death ligands 1 and 2 (PD-L1 and PD-L2). Cancer cells can also produce acetylcholine (ACh), which plays a role in tumor development. Moreover, tumor innervation can stimulate vascularization leading to tumor growth and metastasis. The effects of atropine and muscarinic receptor 3 (M3R) blocker, 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP), on cancer growth and spread were evaluated in vitro using murine colon cancer cell line, CT-26, and in vivo in an orthotopic mouse model of colorectal cancer. In the in vitro model, atropine and 4-DAMP significantly inhibited CT-26 cell proliferation in a dose dependent manner and induced apoptosis. Atropine attenuated immunosuppressive markers and M3R via inhibition of EGFR/AKT/ERK signaling pathways. However, 4-DAMP showed no effect on the expression of PD-L1, PD-L2, and choline acetyltransferase (ChAT) on CT-26 cells but attenuated M3R by suppressing the phosphorylation of AKT and ERK. Blocking of M3R in vivo decreased tumor growth and expression of immunosuppressive, cholinergic, and angiogenic markers through inhibition of AKT and ERK, leading to an improved immune response against cancer. The expression of immunosuppressive and cholinergic markers may hold potential in determining prognosis and treatment regimens for colorectal cancer patients. This study’s results demonstrate that blocking M3R has pronounced antitumor effects via several mechanisms, including inhibition of immunosuppressive molecules, enhancement of antitumor immune response, and suppression of tumor angiogenesis via suppression of the AKT/ERK signaling pathway. These findings suggest a crosstalk between the cholinergic and immune systems during cancer development. In addition, the cholinergic system influences cancer evasion from the host’s immunity. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 24010596 1422-0067 1661-6596 |
| Relation: | https://www.mdpi.com/1422-0067/24/1/596; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
| DOI: | 10.3390/ijms24010596 |
| URL الوصول: | https://doaj.org/article/5a1d0c09b69b4055bce94ab8989c1b73 |
| رقم الأكسشن: | edsdoj.5a1d0c09b69b4055bce94ab8989c1b73 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 24010596 14220067 16616596 |
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| DOI: | 10.3390/ijms24010596 |