Enhancement of antitumor activity of anticancer drugs and irradiation in head and neck cancer

已有报道称，自由基在辐照或tnf诱导细胞凋亡中起一定作用。然而，人体有这些自由基的清除剂。在本研究中，我们试图研究这些清除剂的抑制作用，特别是对清除氧自由基的细胞质Cu、Zn-SOD的抑制作用，以及诱导细胞凋亡的作用。光镜下观察到凋亡小体的形成，琼脂糖凝胶电泳检测到DNA的断裂，证实了细胞凋亡。DDC处理导致SOD活性显著降低。随着SOD活性的降低，凋亡小体出现的频率增加。NAC预处理可降低DDC诱导的细胞凋亡。上述结果提示，胞浆内氧自由基的升高相对于Cu、Zn-SOD活性的降低可能导致细胞凋亡的发生。一些恶性肿瘤对tnf - α或几种由自由基介导的抗肿瘤药物具有抗肿瘤作用。这种抗性的一个预测原因是线粒体酶Mn-SOD的诱导，该酶通过tnf - α清除O_2自由基。我们研究了抑制这种诱导是否能恢复tnf - α的抗肿瘤作用。在含有tnf - α的培养基中培养的细胞株中，没有死细胞。tnf - α的加入显著提高了Mn-SOD的浓度和活性，表明tnf - α在细胞株中诱导了Mn-SOD。这种诱导作用被添加抑制剂所抑制。在添加抑制剂后进一步添加tnf - α，导致50.3%的细胞死亡。

It has been reported that radicals play some role in the induction of apoptosis by irradiation or TNFa. However, the body has scavengers of these radicals. In the present study, we attempted to investigate the effect of inhibition of these scavengers, particularly of cytoplasmic Cu, Zn-SOD that scavenge oxygen radicals, and the induction of apoptosis. Apoptosis was confirmed by the formation of an apoptosis body observed by light microscopy and fragmentation of DNA detected by agarose gel electrophoresis. Treatment of DDC caused a significant decrease in SOD activity. As the SOD activity decreased, the appearance of an apoptosis body increased in frequency. Pretreatment of NAC decreased induction of apoptosis by DDC.The above results suggested that elevation of intracytoplasmic oxygen radicals relative to decrease in the activity of Cu, Zn-SOD may lead to the induction of apoptosis.Some malignant tumors are resistant to TNF-alpha or several antineoplastic agents which exert antitumoral effects mediated by the radicals. One predicted reason for this resistance is induction of an mitochondrial enzyme, Mn-SOD,which scavenges O_2 radicals by TNF-alpha. We investigated whether or not inhibition of this induction recovers the antitumoral effects of TNF-alpha. In the cell strain cultivated in a medium containing TNF-alpha, there were no dead cells. Addition of TNF-alpha significantly increased both the concentration and activity of Mn-SOD,which indicated the induction of Mn-SOD by TNF-alpha in the cell strain. This induction was inhibited by the addition of inhibitor. Further addition of TNF-alpha after the addition of inhibitor caused cell death in 50.3% of the cells.