Sadzuka Y, Mochizuki E, Takino Y
School of Pharmaceutical Sciences, University of Shizuoka.
Jpn J Cancer Res. 1993 Mar;84(3):348-53. doi: 10.1111/j.1349-7006.1993.tb02877.x.
To improve both the survival and the response rate of patients, it is necessary to find modifiers which enhance the effects of known anticancer agents. In this study, we examined the effects of caffeine on the antitumor activity and side effects of antitumor agents, using CDF1 male mice. The combination of caffeine with adriamycin significantly enhanced the antitumor activity of adriamycin, by 1.5-fold and 1.9-fold in single- and multi-administration schedules, respectively, compared to the activity of adriamycin only. However, the combination of caffeine with cisplatin had no effect on the antitumor activity of cisplatin in either administration schedule. We examined two biochemical parameters, lipid peroxide level and glutathione peroxidase activity, as indices of adriamycin-induced side effects. The caffeine combination did not enhance the adriamycin-induced changes in these two parameters. Regarding the lethal effect of adriamycin, the caffeine combination had no effect in the single administration schedule, but in the multi-administration schedule, it tended to reduce this acute toxicity. These results suggest that the combination of caffeine with adriamycin can significantly increase the in vivo antitumor activity of this agent without increasing its side effects.
为了提高患者的生存率和缓解率，有必要找到能够增强已知抗癌药物疗效的修饰剂。在本研究中，我们使用CDF1雄性小鼠，研究了咖啡因对抗肿瘤药物的抗肿瘤活性和副作用的影响。与单独使用阿霉素相比，咖啡因与阿霉素联合使用分别在单次给药和多次给药方案中显著增强了阿霉素的抗肿瘤活性，增幅分别为1.5倍和1.9倍。然而，在两种给药方案中，咖啡因与顺铂联合使用对顺铂的抗肿瘤活性均无影响。我们检测了两个生化参数，即脂质过氧化物水平和谷胱甘肽过氧化物酶活性，作为阿霉素诱导的副作用指标。咖啡因联合使用并未增强阿霉素诱导的这两个参数的变化。关于阿霉素的致死效应，咖啡因联合使用在单次给药方案中无影响，但在多次给药方案中，它倾向于降低这种急性毒性。这些结果表明，咖啡因与阿霉素联合使用可显著提高该药物的体内抗肿瘤活性，而不增加其副作用。
