摘要
目的:既往研究表明益气扶正中药(YQFZ)联合化疗对非小细胞肺癌有较好的协同作用,本研究进一步从线粒体相关分子调控效应揭示益气扶正中药(YQFZ)干预肺癌耐药的机制。方法:通过流式细胞仪观察肺癌耐药细胞SW1573/2R120,分别给予YQFZ和阿霉素(Dox)处理后细胞凋亡改变,原子力显微镜观察细胞超微结构变化,生物氧耗电极检测器测定线粒体氧化磷酸化功能,流式细胞仪检测多药耐药相关蛋白MRP蛋白表达,共聚焦显微镜测定线粒体膜电位MMP、ROS和胞内Xa^(2+)浓度,酶标法测定Caspase-3和Caspase-8活性。结果:YQFZ中药明显增加Dox对肺癌耐药细胞的体外诱导凋亡作用,YQFZ/Dox组细胞早期杀伤的超微结构变化明显,YQFZ显著增加Dox所致的线粒体氧化磷酸化功能损伤作用,YQFZ/Dox组S3值、RCI值和ADP/O值分别明显下降57.1%、53.8%和48.3%,YQFZ/Dox组MRP蛋白表达降低,线粒体膜电位水平减低,ROS和胞内Ca^(2+)浓度减少.Caspase-3和Caspase-8活性明显增高1.64倍和1.13倍。结论:益气扶正中药具有显著干预肺癌耐药的作用,并通过线粒体相关分子效应协同Dox,参与对肺癌耐药细胞的体外诱导凋亡作用。
Objective： To investigate the effects of Chinese herbs of strengthening and invigorating genuine qi on multidrug resistant lung cancer through regulating mitochondria related molecules. Methods： The multidrug resistant lung cancer cell line SW1573/2R120 was treated with YQFZ and Doxorubicin （Dox）, in vitro. Flow cytometry was used to detect apoptosis and MRP expression. Cellular ultrastructure was observed with atomic force microscopy. Mitochondrial oxidative phosphorylation was tested using a biological oxygen monitor. Mitochondrial membrane potential, ROS and intracellular Ca^2＋ concentration were detected using laser scanning confocal microscopy. Caspase-3 and Caspase-8 activity were detected by enzyme-linked immunosorbent assay （ELISA）. Results： Obviously enhanced Dox apoptotic effect was observed, in the Chinese herbs/Dox group, distinct early apoptotic ultrastructural changes were observed. Chinese herbs increased the Dox induced injuries to mitochondrial oxidative phosphorylation. The values of S3, RCI and ADP/O were reduced by 57.1%, 53.8% and 48.3%, respectively, in the Chinese herbs/Dox group. This group also showed reduced MRP expression, mitochonddal membrane potential, ROS and intracellular Ca2. concentration and increased Caspase-3 and Caspase-8 activity by 1.64 folds and 1.13 folds. Conclusion： Chinese herbs of strengthening and invigorating genuine qi can obviously interfere with the drug resistance of lung cancer cells and have a synergistic effect with Dox on promoting apoptosis through regulating mitochondrial molecules.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2010年第13期725-728,共4页
Chinese Journal of Clinical Oncology
基金
国家自然科学基金(编号:30772844)
中国临床肿瘤学科学基金(2005)资助~~
关键词
益气扶正中药
肺癌
化疗
氧化磷酸化
Chinese herbs
L.ung cancer
Chemotherapy
Oxidation phosphorylation
