The Adenosine-A2a Receptor Regulates the Radioresistance of Gastric Cancer Via PI3K-AKT-mTOR Pathway

Overview

Journal Int J Clin Oncol

Specialty Oncology

Date 2022 Feb 5

PMID 35122587

Authors

Guihong Liu

Song Yang

Yang Liu

Yumei Xu

Hui Qiu

Jian Sun

Jun Song

Linsen Shi

Affiliations

Soon will be listed here.

Abstract

Background: Radiotherapy is a key strategy in gastric cancer (GC) treatment. However, radioresistance remains a serious concern. It is unclear whether the accumulation of adenosine A2a receptor (ADO-A2aR) is related to radioresistance in GC. In this study, the molecular role of ADO-A2aR in GC radioresistance was investigated.

Methods: Colony formation assays were used to assess the role of ADO-A2aR on radioresistance. GC stem cell surface marker expression (including Nanog, OCT-4, SOX-2 and CD44) and PI3K/AKT/mTOR signaling pathway associated protein levels (including phosphorylated PI3K, phosphorylated AKT and phosphorylated mTOR) were determined via western blotting, flow cytometry and immunofluorescence. In addition, the role of ADO-A2aR on radioresistance was explored in vivo using murine xenograft models.

Results: ADO-A2aR regulated GC cell stemness both in vitro and in vivo. This was shown to induce radioresistance in GC. ADO-A2aR was revealed to significantly induce cell cycle arrest and promote GC cell apoptosis. These activities were closely linked to activation of the PI3K/AKT/mTOR pathway.

Conclusion: This study identified that ADO enhances GC cell stemness via interaction with A2aR and subsequent activation of the PI3K/AKT/mTOR pathway. Ultimately, this resulted in radioresistance. A2aR is a potential target to improve GC radiosensitivity.

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