Details

Autor(en) / Beteiligte

• Liu, Guihong
• Yang, Song
• Liu, Yang
• Xu, Yumei
• Qiu, Hui
• Sun, Jian
• Song, Jun
• Shi, Linsen

Titel

The adenosine-A2a receptor regulates the radioresistance of gastric cancer via PI3K-AKT-mTOR pathway

Ist Teil von

• International journal of clinical oncology, 2022-05, Vol.27 (5), p.911-920

Ort / Verlag

Singapore: Springer Nature Singapore

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.