Yu Biying, Yang Hongqin, Zhang Xiaoman, Li Hui
1 Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Fujian Normal University, Fuzhou, China.
Technol Cancer Res Treat. 2018 Jan 1;17:1533033818785274. doi: 10.1177/1533033818785274.
Heat shock protein 70 has been recognized as a target for anticancer therapy. The overexpression of heat shock protein 70 is observed frequently in several types of tumors, including breast cancer. It is involved with increased cell proliferation, poor prognosis, and drug resistance in breast cancer. VER-155008 is an effective inhibitor of heat shock protein 70 that targets the adenosine triphosphatase-binding domain of heat shock protein 70. In this study, the effects of VER-155008, heat shock (43°C, 1 hour), and the combination treatment of VER-155008 and heat shock on the mitochondria of the MCF-7 breast cancer cells were investigated through a laser scanning microscope combined with mitochondrial membrane potential fluorescence probe. We observed broken mitochondria networks, decreased mitochondrial membrane potential, and cell size. The mitochondrial contents were reduced with the VER-155008 treatment and the combination treatment of VER-155008 and heat shock. The effects of the inhibition presented treatment time dependence. Moreover, the effect of the inhibition of the sole VER-155008 was alleviated when it was combined with heat shock although there was no obvious change with the sole heat shock treatment. The results indicated that VER-155008, the inhibitor of heat shock protein 70, induced apoptosis in MCF-7 breast cancer cells whatever it was in the sole or the combined manner, and its promoting apoptosis effect could be alleviated by heat shock. Our findings demonstrated that HSP70 can be a good target for developing breast cancer therapy.
热休克蛋白70已被公认为抗癌治疗的靶点。热休克蛋白70的过表达在包括乳腺癌在内的多种肿瘤类型中经常被观察到。它与乳腺癌中细胞增殖增加、预后不良和耐药性有关。VER-155008是一种有效的热休克蛋白70抑制剂,靶向热休克蛋白70的三磷酸腺苷结合结构域。在本研究中,通过激光扫描显微镜结合线粒体膜电位荧光探针,研究了VER-155008、热休克(43°C,1小时)以及VER-155008与热休克联合处理对MCF-7乳腺癌细胞线粒体的影响。我们观察到线粒体网络断裂、线粒体膜电位降低以及细胞大小改变。VER-155008处理以及VER-155008与热休克联合处理均使线粒体含量减少。抑制作用呈现出处理时间依赖性。此外,尽管单独热休克处理没有明显变化,但VER-155008与热休克联合处理时,单独使用VER-155008的抑制作用有所减轻。结果表明,热休克蛋白70抑制剂VER-155008无论单独使用还是联合使用,均可诱导MCF-7乳腺癌细胞凋亡,且热休克可减轻其促凋亡作用。我们的研究结果表明,HSP70可以成为开发乳腺癌治疗方法的良好靶点。