Salvianolic acid B renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction
Salvianolic acid B renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction
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DOI：
10.1016/j.biopha.2018.08.113
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发表时间：
2018-11-01
影响因子：
7.5
通讯作者：
Wang, Mao-De
中科院分区：
文献类型：
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作者：
Chen, Wei;Wang, Ning;Wang, Mao-De
神经胶质瘤仍然是全球脑肿瘤相关死亡的主要原因，放射治疗是一种标准的辅助治疗方法，疗效已得到证实。丹参酸B（SalB）是从丹参中分离得到的一种生物活性化合物，对多种肿瘤细胞具有抗肿瘤作用，包括胶质瘤。本研究旨在探讨SalB是否影响人脑胶质瘤细胞对辐射的反应。我们发现SalB以剂量依赖的方式降低U87细胞的细胞活力。阈下剂量的SalB在0.5 μ M，这对细胞活力和凋亡没有影响，显着增加辐射敏感性的U87细胞的剂量和时间依赖性的方式，但对替莫唑胺（TMZ）的敏感性没有影响。在人胶质瘤U373细胞中也观察到类似的结果。此外，通过线粒体Ca 2+缓冲能力和线粒体肿胀来衡量，SalB加剧了辐射诱导的细胞凋亡和线粒体功能障碍。SalB处理显著促进线粒体分裂，并对分裂蛋白的表达有不同程度的调节。此外，使用siRNA下调裂变蛋白Fis-1被发现部分逆转SalB诱导的U87细胞中细胞活力、凋亡和线粒体分裂的影响。总之，我们的研究结果表明，阈下剂量的SalB通过Fis-1介导的线粒体功能障碍使胶质瘤细胞对辐射更敏感，放射治疗结合SalB可能是胶质瘤患者的一种新的治疗方法。
Glioma remains the leading cause of brain tumor-related death worldwide, and radiation is a standard adjuvant therapy with proven efficacy. Salvianolic acid B (SalB), a bioactive compound isolated from Radix Salviae, has been shown to exert anti-cancer effects in many cancer cell lines, including glioma. This study aimed to investigate whether SalB could affect response to radiation in human glioma cells. We found that SalB decreased cell viability of U87 cells in a-dose-dependent manner. A subthreshold dose of SalB at 0.5 mu M, which had no effect on cell viability and apoptosis, significantly increased radiation sensitivity of U87 cells in a dose-and time-dependent manner, but had no effect on sensitivity to temozolomide (TMZ). Similar results were also observed in human glioma U373 cells. In addition, SalB aggravated the radiation-induced apoptosis and mitochondrial dysfunction, as measured by mitochondrial Ca2+ buffering capacity and mitochondrial swelling. SalB treatment markedly promoted mitochondrial fission and differently regulated the expression of fission proteins. Furthermore, downregulation of the fission protein Fis-1 using siRNA was found to partially reversed the SalB-induced effects on cell viability, apoptosis and mitochondrial fission in U87 cells. In conclusion, our results suggest that a subthreshold dose of SalB renders glioma cells more sensitive to radiation via Fis-1-mediated mitochondrial dysfunction, and radiotherapy combined with SalB might be a novel treatment for glioma patients.