SOD对肿瘤细胞凋亡影响和抗氧化损伤的研究:Ⅰ.SOD与DDP、ADM、VP16合用对肿瘤细胞凋亡的影响

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将顺铂(DDP)、阿霉素(ADM)和足叶乙甙(VP16)以不同时间作用于实验小鼠宫颈癌Hela细胞,测定细胞内活性氧(ROS)水平和细胞凋亡率,研究抗肿瘤药物诱导Hela细胞凋亡与细胞内ROS水平的关系。研究表明,在抗肿瘤药物作用前加入超氧化物歧化酶(SOD),会减少Hela细胞的凋亡,在抗肿瘤药物作用24h后加入SOD,对Hela细胞的凋亡无影响,而且对Hela细胞p53、c?fos基因产物表达也无影响。荷瘤小鼠机体整体水平研究表明,在给予化疗药物4h后连续5d注入SOD,与单纯化疗药物组相比,可显著减少荷瘤小鼠骨髓细胞,肝脏和脾脏组织匀浆中ROS水平。表明后注入SOD可直接清除重要脏器细胞内因化疗药物产生的过量ROS,还可提高其它抗氧化酶活性而协同清除化疗药物产生的过量ROS,从而避免正常器官的氧化性损伤。本研究结果为肿瘤化疗中适时施用SOD,减少化疗的毒副作用具有一定指导意义。 The effects of DDP, ADM and VP16 on Hela cells in vitro and in vivo were observed and the levels of reactive oxygen species (ROS) and apoptosis were determined. Relationship between HeLa Cell Apoptosis and Intracellular ROS Level Induced by Antitumor Drugs. Studies have shown that the addition of superoxide dismutase (SOD) before the antitumor drugs can reduce the apoptosis of Hela cells. After the antitumor drugs act for 24 hours, the addition of SOD has no effect on the apoptosis of Hela cells, p53, c? fos gene product expression also had no effect. Tumor-bearing mice overall body level studies showed that 4h after the administration of chemotherapy drugs into the continuous 5d SOD, compared with the chemotherapy alone group, can significantly reduce tumor-bearing mice bone marrow cells, liver and spleen tissue ROS levels. After injection of SOD, it can directly eliminate excess ROS generated by chemotherapeutic drugs in cells of vital organs. It can also increase the activity of other antioxidant enzymes and synergistically eliminate excessive ROS generated by chemotherapeutic drugs to prevent the oxidative damage of normal organs. The results of this study for the timely application of chemotherapy in tumor chemotherapy, reduce the side effects of chemotherapy has a guiding significance.
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