College of Computer and Information Science, Southwest University, Chongqing 400715, China.
College of Computer Science, Sichuan University, Chengdu 610065, China.
Int J Mol Sci. 2019 Sep 19;20(18):4643. doi: 10.3390/ijms20184643.
Glioma is the most aggressive and lethal brain tumor in humans. Mutations of mitochondrial DNA (mtDNA) are commonly found in tumor cells and are closely associated with tumorigenesis and progress. However, glioma-specific inhibitors that reflect the unique feature of tumor cells are rare. Here we uncover RC-7, a ruthenium complex with strong red fluorescence, could bind with glioma mtDNA and then inhibited the growth of human glioma cells but not that of neuronal cells, liver, or endothelial cells. RC-7 significantly reduced energy production and increased the oxidative stress in the glioma cells. Administration of RC-7 into mice not only could be observed in the glioma mass of brain by fluorescence imaging, but also obviously prevented the growth of xenograft glioma and prolonged mouse survival days. The findings suggested the theranostic application of a novel type of complex through targeting the tumor mtDNA.
胶质母细胞瘤是人类最具侵袭性和致命性的脑肿瘤。线粒体 DNA（mtDNA）的突变在肿瘤细胞中很常见，与肿瘤发生和进展密切相关。然而，反映肿瘤细胞独特特征的胶质母细胞瘤特异性抑制剂却很少见。在这里，我们发现 RC-7 是一种具有强红色荧光的钌配合物，它可以与胶质母细胞瘤 mtDNA 结合，然后抑制人胶质母细胞瘤细胞的生长，但不抑制神经元细胞、肝脏或内皮细胞的生长。RC-7 显著降低了能量产生，并增加了胶质母细胞瘤细胞中的氧化应激。将 RC-7 给药到小鼠体内，不仅可以通过荧光成像观察到脑内的胶质母细胞瘤肿块，而且还明显阻止了异种移植胶质母细胞瘤的生长并延长了小鼠的存活天数。这些发现表明，通过靶向肿瘤 mtDNA，新型配合物具有治疗诊断应用的潜力。
