Tang Shaokai,Chen Jianhui,Geng Fenghao,Yang Tingyi,Li Xiaoqian,Du Xiaobo,Zhang Shuyu.The radiosensitization effect of STING agonist on cutaneous melanoma cells[J].Chinese Journal of Radiological Medicine and Protection,2023,43(1):1-7
The radiosensitization effect of STING agonist on cutaneous melanoma cells
Received:August 26, 2022  
DOI:10.3760/cma.j.cn112271-20220826-00350
KeyWords:Cutaneous melanoma  Stimulator of interferon gene  Radiosensitivity
FundProject:国家自然科学基金(82073477);四川省杰出青年科技人才项目(2022JDJQ0051);四川大学-泸州科技创新研发项目(2021CDLZ-9)
Author NameAffiliationE-mail
Tang Shaokai Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China  
Chen Jianhui Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China  
Geng Fenghao Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China  
Yang Tingyi Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China  
Li Xiaoqian Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China  
Du Xiaobo NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, Mianyang 621099, China  
Zhang Shuyu Laboratory of Radiation Medicine, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, China zhang.shuyu@hotmail.com 
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Abstract::
      Objective To investigate the radiosensitizing effect and underlying mechanism of STING agonist (c-di-AMP) on cutaneous melanoma cells.Methods Human cutaneous melanoma cells (A375) were divided into four groups: the control group, 10 μmol/L c-di-AMP group, X-ray irradiation group and X-ray irradiation combined with c-di-AMP group. The radiosensitizing effect of c-di-AMP on A375 cells was detected by CCK-8-based viability assay, lactate dehydrogenase (LDH) release assay, flow cytometry-based apoptosis assay, and colony formation assay. Western blot analysis was used to determine the expressions of cell death-related proteins.Results In combination with 10 Gy X-ray irradiation, 10 μmol/L c-di-AMP showed significant radiosensitization effect in A375 cells, which was evidenced by decreased cell activity (t=5.11, P<0.05), increased cytotoxicity (t=10.15, P<0.05) and cell apoptosis (t=4.41, P<0.05) and reduced clone viability(t=6.30, 3.55, 5.45, 3.55, P<0.05). The calculated radiosensitization ratio of c-di-AMP to A375 cells was 1.88. Moreover, 10 μmol/L c-di-AMP further increased the expressions of cell death-related proteins induced by radiation in A375 cells.Conclusions The STING agonist c-di-AMP can be used as a radiosensitizer for cutaneous melanoma, which may provide a novel strategy for radiotherapy.
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