Sadzuka Y, Iwazaki A, Hirota S
School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Yakugaku Zasshi. 1998 May;118(5):179-87. doi: 10.1248/yakushi1947.118.5_179.
The antitumor activity of adriamycin (ADR) was enhanced by combination with theobromine or pentoxifylline. Theobromine increased the concentration of ADR in the tumor without any effects on that in the heart and the liver. The influence of the combination of theobromine or pentoxifylline with ADR on the lipid peroxide level (indicating the ADR-induced side effect) and on DNA biosynthesis (indicating the side effect and antitumor activity) were examined. When ADR was administered into mice, the lipid peroxide level in the liver and the heart increased. However, the combination of theobromine or pentoxifylline did not enhance the ADR-induced increment of the lipid peroxide level in the liver, and moreover, it inhibited that in the heart. The decrease of DNA biosynthesis in the liver and the heart, induced by ADR, were not enhanced by combination with theobromine or pentoxifylline. On the other hand, the combination of theobromine with ADR significantly increased the inhibition of DNA biosynthesis in the tumor. These findings indicate that the combination of theobromine or pentoxifylline with ADR have no effect on the side effects of ADR in the liver and the heart, with the increase of antitumor activity of ADR in the tumor, and it is suggested that these drugs will be of value as a biochemical modulator of ADR.
阿霉素（ADR）与可可碱或己酮可可碱联合使用时，其抗肿瘤活性增强。可可碱可提高肿瘤中阿霉素的浓度，而对心脏和肝脏中的阿霉素浓度无任何影响。研究了可可碱或己酮可可碱与阿霉素联合使用对脂质过氧化物水平（表明阿霉素诱导的副作用）和DNA生物合成（表明副作用和抗肿瘤活性）的影响。给小鼠注射阿霉素后，肝脏和心脏中的脂质过氧化物水平升高。然而，可可碱或己酮可可碱联合使用并未增强阿霉素诱导的肝脏脂质过氧化物水平的升高，而且还抑制了心脏中的升高。阿霉素诱导的肝脏和心脏中DNA生物合成的减少，与可可碱或己酮可可碱联合使用时并未增强。另一方面，可可碱与阿霉素联合使用显著增加了肿瘤中DNA生物合成的抑制作用。这些发现表明，可可碱或己酮可可碱与阿霉素联合使用对阿霉素在肝脏和心脏中的副作用无影响，同时增加了阿霉素在肿瘤中的抗肿瘤活性，提示这些药物作为阿霉素的生化调节剂具有一定价值。
