| 唐绍凯,陈建辉,耿凤豪,杨婷仪,李晓倩,杜小波,张舒羽.干扰素基因激活因子激动剂对人皮肤黑色素瘤细胞的放射增敏作用研究[J].中华放射医学与防护杂志,2023,43(1):1-7 |
| 干扰素基因激活因子激动剂对人皮肤黑色素瘤细胞的放射增敏作用研究 |
| The radiosensitization effect of STING agonist on cutaneous melanoma cells |
| 投稿时间：2022-08-26 |
| DOI：10.3760/cma.j.cn112271-20220826-00350 |
| 中文关键词: 皮肤黑色素瘤 干扰素基因激活因子 放射敏感性 |
| 英文关键词:Cutaneous melanoma Stimulator of interferon gene Radiosensitivity |
| 基金项目: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) |
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| 中文摘要: |
| 目的 探讨干扰素基因激活因子(STING)激动剂对皮肤黑色素瘤细胞的放射增敏作用及其机制。方法 为检测STING激动剂环二腺苷酸(c-di-AMP)对人皮肤黑色素瘤细胞(A375)辐射后的影响,将人皮肤黑色素瘤细胞A375分为空白对照组、10μmol/L c-di-AMP处理组、X射线照射组、照射+c-di-AMP组。通过CCK-8法、乳酸脱氢酶(LDH)释放实验、平板克隆形成实验以及流式细胞术等手段,检测c-di-AMP对A375细胞的放射增敏作用。采用Western blot检测细胞死亡相关蛋白表达。结果 10μmol/L的c-di-AMP联合10 Gy X射线照射时可见明显的放射增敏效应,A375细胞活力较X射线照射组显著下降(t=5.11,P<0.05),细胞毒性显著增加(t=10.15,P<0.05),细胞凋亡显著增加(t=4.41,P<0.05),细胞克隆增殖能力显著降低(t=6.30、3.55、5.45、3.55,P<0.05)。c-di-AMP的放射增敏比(SER)为1.88。10μmol/L的c-di-AMP联合10 Gy X射线后细胞死亡相关信号通路(细胞凋亡、细胞坏死、铁死亡)相关蛋白表达较X射线照射组显著上调。结论 采用c-di-AMP激活STING可显著增加电离辐射对皮肤黑色素瘤的放射敏感性,为皮肤黑色素瘤放射治疗提供了新的策略。 |
| 英文摘要: |
| 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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