AI Article Synopsis
- Cholangiocarcinoma (CCA) has a poor outlook and limited treatment options; this study explores the role of adiponectin and AMPK signaling in CCA, specifically focusing on the effects of AdipoRon, an adiponectin receptor agonist.
- The study found that AdipoR1 and p-AMPKα levels were lower in CCA tissues, with AdipoRon treatment leading to reduced tumor growth, migration, and increased cell death both in lab tests and in mouse models.
- The findings suggest that targeting adiponectin signaling with AdipoRon could be a promising new approach for treating CCA, potentially providing a new anti-tumor therapy.
Article Abstract
Background: Cholangiocarcinoma (CCA) has a poor prognosis and only limited palliative treatment options. The deficiency of adiponectin and adenosine monophosphate-activated protein kinase (AMPK) signaling was reported in several malignancies, but the alteration of these proteins in CCA is still unclear.
Objectives: This study aimed to assess the role of adiponectin and AMPK signaling in CCA. Furthermore, AdipoRon, a novel adiponectin receptor (AdipoR) agonist, was evaluated in vitro and in vivo as a new anti-tumor therapy for CCA.
Methods: The expression of AdipoR1 and p-AMPKα in human tissue microarrays (TMAs) was evaluated by immunohistochemistry staining (IHC). The effect of 2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide (AdipoRon) was investigated in vitro with proliferation, crystal violet, migration, invasion, colony formation, senescence, cell cycle and apoptosis assays and in vivo using a CCA engineered mouse model (AlbCre/LSL-KRAS/p53). RT-qPCR and western blot methods were applied to study molecular alterations in murine tissues.
Results: AdipoR1 and p-AMPKα were impaired in human CCA tissues, compared to adjacent non-tumor tissue. There was a positive correlation between the AdipoR1 and p-AMPKα levels in CCA tissues. Treatment with AdipoRon inhibited proliferation, migration, invasion and colony formation and induced apoptosis in a time- and dose-dependent manner in vitro (p<0.05). In addition, AdipoRon reduced the number of CCA and tumor volume, prolonged survival, and decreased metastasis and ascites in the treated group compared to the control group (p<0.05).
Conclusions: AdipoR1 and p-AMPKα are impaired in CCA tissues, and AdipoRon effectively inhibits CCA in vitro and in vivo. Thus, AdipoRon may be considered as a potential anti-tumor therapy in CCA.
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| http://dx.doi.org/10.2174/0109298673254969231122114107 | DOI Listing |
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