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<p>Conventional therapeutic approaches against colorectal cancer often face limitations. One of the critical pathways implicated in tumor progression is the adenosinergic signaling pathway, which plays a major role in immune suppression within the tumor microenvironment. This investigation aimed to evaluate the effect of resveratrol on adenosine production and its antitumor potential in colon cancer cell lines (CT26 and SW480) under in vitro conditions. In this experimental investigation, human (SW480) and murine (CT26) colon cancer cell lines were subjected to various concentrations of resveratrol to assess its biological impacts. Apoptosis and MTT assays were performed to evaluate cell viability, while quantitative real-time PCR was used to measure the expression levels of A2AR, A2BR, and 5′-nucleotidase (CD73) genes. AMP hydrolysis&#xa0;was conducted for CD73 activity assay. Additionally, the impact of resveratrol on the migratory capacity of the cells was determined by scratch assay. A distinct decline in cell survival was observed with increasing resveratrol concentrations, accompanied by a corresponding rise in apoptotic activity in both CT26 and SW480 cells with IC50 value of 54.2 and 23.2 μM, respectively. In addition, wound closure rates in the scratch assay were markedly decreased following resveratrol exposure, indicating inhibition of cell migration. CD73 enzymatic activity and expression were significantly downregulated, leading to reduced adenosine production. Furthermore, resveratrol dose-dependently inhibited the expression of A2AR and A2BR, suggesting disruption of the adenosinergic signaling pathway. These findings designate that resveratrol has a strong inhibitory effect on colon cancer cells by inhibiting CD73-mediated adenosine production and downregulating adenosine receptor expression.</p>

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Resveratrol-mediated disruption of the CD73–adenosine–A2AR/A2BR axis induces antitumor activity in colon cancer cells

  • 期刊论文

  • 发表日期：

    2026年4月29日

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  • Maryam Talebi,
  • Hossein Dehghan,
  • Ramazan Rezaei

摘要

Conventional therapeutic approaches against colorectal cancer often face limitations. One of the critical pathways implicated in tumor progression is the adenosinergic signaling pathway, which plays a major role in immune suppression within the tumor microenvironment. This investigation aimed to evaluate the effect of resveratrol on adenosine production and its antitumor potential in colon cancer cell lines (CT26 and SW480) under in vitro conditions. In this experimental investigation, human (SW480) and murine (CT26) colon cancer cell lines were subjected to various concentrations of resveratrol to assess its biological impacts. Apoptosis and MTT assays were performed to evaluate cell viability, while quantitative real-time PCR was used to measure the expression levels of A2AR, A2BR, and 5′-nucleotidase (CD73) genes. AMP hydrolysis was conducted for CD73 activity assay. Additionally, the impact of resveratrol on the migratory capacity of the cells was determined by scratch assay. A distinct decline in cell survival was observed with increasing resveratrol concentrations, accompanied by a corresponding rise in apoptotic activity in both CT26 and SW480 cells with IC50 value of 54.2 and 23.2 μM, respectively. In addition, wound closure rates in the scratch assay were markedly decreased following resveratrol exposure, indicating inhibition of cell migration. CD73 enzymatic activity and expression were significantly downregulated, leading to reduced adenosine production. Furthermore, resveratrol dose-dependently inhibited the expression of A2AR and A2BR, suggesting disruption of the adenosinergic signaling pathway. These findings designate that resveratrol has a strong inhibitory effect on colon cancer cells by inhibiting CD73-mediated adenosine production and downregulating adenosine receptor expression.