Wessels Johannes Theodor, Busse Ann-Christin, Rave-Fränk Margret, Zänker Stephan, Hermann Robert, Grabbe Eckhardt, Müller Gerhard-Anton
Center of Internal Medicine, Department of Nephrology/Rheumatology, University Hospital, Göttingen, Germany.
Photochem Photobiol. 2008 Jan-Feb;84(1):228-35. doi: 10.1111/j.1751-1097.2007.00225.x.
The renal cell carcinoma (RCC) is extremely resistant to chemotherapy and radiotherapy. The prognosis of patients with metastatic RCC still remains poor, the median survival is less than 12 months. Therefore, new therapeutic options are desirable. The aim of this study was to investigate the photosensitizing and radiosensitizing effects of hypericin on human RCC cells in vitro. First the RCC-derived cell lines A498 and ACHN were incubated with different concentrations of hypericin. In vitro uptake and intracellular distribution of hypericin were confirmed by fluorescence microscopy. Subsequently cells were illuminated and irradiated with a dose of 2-8 Gy, respectively. Finally, metabolic activity, apoptosis and clonogenic survival were investigated. Uptake of hypericin was observed for almost all cells. Hypericin treatment combined with illumination led to a 94-97% decrease in metabolic activity and caused apoptosis in nearly 100% of RCC cells. Hypericin enhanced the radiosensitivity of A498 cells in vitro. The clonogenic survival after irradiation was significantly reduced by hypericin treatment. Taken together, the photosensitizing and radiosensitizing effects of hypericin on human RCC cells we found in this investigation could be of clinical relevance, e.g. for radiotherapy and intraoperative photodynamic therapy, respectively.
肾细胞癌（RCC）对化疗和放疗极具抗性。转移性肾细胞癌患者的预后仍然很差，中位生存期不到12个月。因此，需要新的治疗选择。本研究的目的是在体外研究金丝桃素对人肾癌细胞的光敏和放射增敏作用。首先，将源自肾细胞癌的细胞系A498和ACHN与不同浓度的金丝桃素孵育。通过荧光显微镜确认金丝桃素的体外摄取和细胞内分布。随后，分别用2-8 Gy的剂量对细胞进行光照和照射。最后，研究代谢活性、细胞凋亡和克隆形成存活率。几乎所有细胞均观察到金丝桃素的摄取。金丝桃素处理联合光照导致代谢活性降低94-97%，并使近100%的肾癌细胞发生凋亡。金丝桃素在体外增强了A498细胞的放射敏感性。经金丝桃素处理后，照射后的克隆形成存活率显著降低。综上所述，我们在本研究中发现的金丝桃素对人肾癌细胞的光敏和放射增敏作用可能具有临床意义，例如分别用于放疗和术中光动力治疗。
