Involvement of A2B Receptor in DNA Damage Response and Radiosensitizing Effect of A2B Receptor Antagonists on Mouse B16 Melanoma.

Abstract:

:It is therapeutically important to elucidate the factors involved in the radiation resistance of tumors. We previously showed that ATP is released from mouse melanoma B16 cells in response to γ-irradiation, but the role of adenosine, a metabolite of ATP, is still unclear. Here, we show that the adenosine A2B receptor is involved in DNA damage repair and radioresistance in mouse melanoma B16 cells. The DNA damage response after γ-irradiation was attenuated by pretreatment with A2B receptor antagonists, such as PSB603, while it was enhanced by pretreatment with A2B receptor agonists, such as BAY60-6583. γ-Irradiation decreased the cell survival rate, and pretreatment with PSB603 further reduced the survival rate. On the other hand, pretreatment with BAY60-6583 increased the cell survival rate after irradiation. The DNA damage response and the cell survival rate after γ-irradiation were both decreased in A2B-knockdown cells. In vivo experiments in mice confirmed that tumor growth was suppressed and delayed in the irradiated group pretreated with PSB603, compared with the irradiation-alone group. Our results indicate that adenosine A2B receptor contributes to radioresistance, and could be a new target for the development of agents to increase the efficacy of radiotherapy.

journal_name

Biol Pharm Bull

authors

Tanaka Y,Kitabatake K,Abe R,Tsukimoto M

doi

10.1248/bpb.b19-00976

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

516-525

issue

3

eissn

0918-6158

issn

1347-5215

journal_volume

43

pub_type

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