徐 萌, 张国军, 潘兰红, 盛良翮, 朱新海, 曾世彬, 池德祥. 益气扶正中药对肺癌耐药调控的线粒体相关分子效应*[J]. 中国肿瘤临床, 2010, 37(13): 725-728. DOI: 10.3969/j.issn.1000-8179.2010.13.002
引用本文: 徐 萌, 张国军, 潘兰红, 盛良翮, 朱新海, 曾世彬, 池德祥. 益气扶正中药对肺癌耐药调控的线粒体相关分子效应*[J]. 中国肿瘤临床, 2010, 37(13): 725-728. DOI: 10.3969/j.issn.1000-8179.2010.13.002
XU Meng, ZHANG Guojun, PAN Lanhong, SHENG Lianghe, ZHU Xinhai, ZENG Shibin, CHI Dexiang. Effects of Chinese Herbs of Strengthening and Invigorating Genuine Qi on Multidrug Resistant  Lung Cancer Cells through Regulation of Mitochondria Related Molecules[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(13): 725-728. DOI: 10.3969/j.issn.1000-8179.2010.13.002
Citation: XU Meng, ZHANG Guojun, PAN Lanhong, SHENG Lianghe, ZHU Xinhai, ZENG Shibin, CHI Dexiang. Effects of Chinese Herbs of Strengthening and Invigorating Genuine Qi on Multidrug Resistant  Lung Cancer Cells through Regulation of Mitochondria Related Molecules[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2010, 37(13): 725-728. DOI: 10.3969/j.issn.1000-8179.2010.13.002

益气扶正中药对肺癌耐药调控的线粒体相关分子效应*

Effects of Chinese Herbs of Strengthening and Invigorating Genuine Qi on Multidrug Resistant  Lung Cancer Cells through Regulation of Mitochondria Related Molecules

  • 摘要: 目的:既往研究表明益气扶正中药(YQF Z)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Ca2 +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Ca2 +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。

     

    Abstract: Objective:To investigate the effects of Chinese herbs of strengthening and invigorating genuine qi on multi -drug 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 apopto-sis and MRP expression. Cellular ultrastructure was observed with atomic force microscopy. Mitochondrial oxidative phos-phorylation was tested using a biological oxygen monitor. Mitochondrial membrane potential, ROS and intracellular Ca2 + 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 S 3, 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, mito-chondrial membrane potential, ROS and intracellular Ca2 + concentration and increased Caspase-3 and Caspase-8 activity by1.64folds and 1.13folds. Conclusion:Chinese herbs of strengthening and invigorating genuine qi can obviously inter-fere with the drug resistance of lung cancer cells and have a synergistic effect with Dox on promoting apoptosis through regulating mitochondrial molecules.

     

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