Han Xiaoyue, Song Xinyu, Yu Fabiao, Chen Lingxin
Key Laboratory of Coastal Environmental Processes and Ecological Remediation , Research Centre for Coastal Environmental Engineering and Technology , Yantai Institute of Coastal Zone Research , Chinese Academy of Sciences , Yantai 264003 , China . Email:
University of Chinese Academy of Sciences , Beijing 100049 , China.
Chem Sci. 2017 Oct 1;8(10):6991-7002. doi: 10.1039/c7sc02888a. Epub 2017 Aug 11.
Hypothermia and hyperthermia are cell stressed states resulting from environmental temperature changes, which can abnormally decrease intracellular glutathione (GSH) concentrations and induce apoptosis. As the most abundant intracellular non-protein biothiol, GSH can protect cells from apoptosis. Considering the important roles of GSH in the anti-apoptotic process in cells and , we strive to develop a powerful chemical tool for the direct detection of GSH concentration changes under temperature stress. Herein, we report a ratiometric fluorescent probe () based on a selenium-sulfur exchange reaction for the qualitative and quantitative detection of GSH concentration fluctuations in cells and . The probe has been successfully used to assess the changes of GSH levels in HepG2 and HL-7702 cells using the stimulations of hypothermia and hyperthermia. In terms of the anti-apoptotic effect of GSH under hypothermic and hyperthermic conditions, human normal liver HL-7702 cells have stronger abilities to fight against temperature stress than human liver carcinoma HepG2 cells. Hypothermia and hyperthermia can also improve the drug resistance of -dichlorodiamineplatinum(ii) (DDP)-resistant HepG2/DDP cells. The probe has been employed to image GSH concentration changes in HepG2 and HepG2/DDP xenografts on nude mice. With the adjuvant therapy effects of hypothermia and hyperthermia, the chemotherapy drug DDP exhibits good ability for the treatment of HepG2 and HepG2/DDP xenografts. The above applications make our probe a potential new candidate for the accurate diagnosis of cancer and efficacy evaluation of treatment.
体温过低和体温过高是由环境温度变化导致的细胞应激状态,可异常降低细胞内谷胱甘肽(GSH)浓度并诱导细胞凋亡。作为细胞内含量最丰富的非蛋白质生物硫醇,GSH可保护细胞免于凋亡。考虑到GSH在细胞抗凋亡过程中的重要作用,我们致力于开发一种强大的化学工具,用于直接检测温度应激下GSH浓度的变化。在此,我们报道了一种基于硒-硫交换反应的比率荧光探针(),用于定性和定量检测细胞内GSH浓度的波动。该探针已成功用于通过低温和高温刺激评估HepG2和HL-7702细胞中GSH水平的变化。就低温和高温条件下GSH的抗凋亡作用而言,人正常肝脏HL-7702细胞比人肝癌HepG2细胞具有更强的抵抗温度应激的能力。低温和高温还可提高顺二氯二氨合铂(II)(DDP)耐药的HepG2/DDP细胞的耐药性。该探针已用于对裸鼠体内HepG2和HepG2/DDP异种移植瘤中GSH浓度变化进行成像。在低温和高温的辅助治疗作用下,化疗药物DDP对HepG2和HepG2/DDP异种移植瘤具有良好的治疗能力。上述应用使我们的探针成为癌症准确诊断和治疗疗效评估的潜在新候选者。