Thews O, Koenig R, Kelleher D K, Kutzner J, Vaupel P
Institute of Physiology and Pathophysiology, Johannes Gutenberg-University, Mainz, Germany.
Br J Cancer. 1998 Sep;78(6):752-6. doi: 10.1038/bjc.1998.572.
The radiosensitivity of solid tumours in anaemic rats treated with recombinant human erythropoietin (rhEPO, epoetin beta) was studied. Anaemia was induced by a single dose of carboplatin (45 mg kg(-1) i.v.), resulting in a reduction in the haemoglobin concentration by 30%. In a second group, the development of anaemia was prevented by rhEPO (1000 IU kg(-1)) administered s.c. three times per week starting 6 days before the carboplatin application. Three days after carboplatin treatment, DS-sarcomas were implanted subcutaneously onto the hind foot dorsum. Neither carboplatin nor rhEPO treatment influenced tumour growth rate. Five days after implantation, tumours were irradiated with a single non-curative dose (10 Gy), resulting in a growth delay with a subsequent regrowth of the tumours. In the rhEPO-treated group, the growth delay lasted significantly longer (9.5 days vs. 4.5 days) and the regrowth was slower (6.0 days vs. 4.1 days) compared with the anaemic group. These data suggest that the correction of chemotherapy-induced anaemia by rhEPO (epoetin beta) treatment increases tumour radiosensitivity, presumably as a result of an improved oxygen supply to tumour tissue.
研究了用重组人促红细胞生成素(rhEPO,β-促红细胞生成素)治疗的贫血大鼠实体瘤的放射敏感性。通过单次静脉注射卡铂(45 mg kg⁻¹)诱导贫血,导致血红蛋白浓度降低30%。在第二组中,从卡铂应用前6天开始,每周皮下注射3次rhEPO(1000 IU kg⁻¹),预防贫血的发生。卡铂治疗3天后,将DS-肉瘤皮下植入后足背部。卡铂和rhEPO治疗均不影响肿瘤生长速度。植入后5天,用单次非治愈剂量(10 Gy)照射肿瘤,导致肿瘤生长延迟,随后肿瘤再生长。与贫血组相比,rhEPO治疗组的生长延迟持续时间明显更长(9.5天对4.5天),再生长速度更慢(6.0天对4.1天)。这些数据表明,通过rhEPO(β-促红细胞生成素)治疗纠正化疗诱导的贫血可提高肿瘤放射敏感性,可能是由于肿瘤组织的氧供应改善所致。