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

Studies on tumor cell apoptosis with SOD and its anti-oxidation effect I. The effect of SOD on apoptosis of tumor cell in DDP, ADM and VP16

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。

By determination of ROS and apoptosis of Hela cells in mice at different hours after treatment with DDP, ADM or VP-16, the relations between apoptosis of Hela cell induced by chemotherapic Drug and concentration of ROS has been investigated. It has been found that there is no effect on apoptosis, and the P53 and c-fos expressions, of the Hela cells when SOD was applied 24 hours after the chemotherapy, whereas apoptosis of the Hela cells reduced when SOD was applied beforethe chemotherapy. Comparing with the control group, to which just ADM and DDP were given, ROS levels reduced markedly in bone marrow, liver and spleen of the tumor-bearing mice, which had been treated with SOD for five consecutive days 4 hours after the chemotherapy. It can be inferred that the oxidation damage of normal tissue can be avoided with scavenge of excessive ROS and increase of anti-oxidative enzymes by SOD in the chemotherapy. The results suggest that injecting SOD at suitable time in clinic chemotherapy may be useful for reducing the side effects.