Kagawa Yoshiyuki, Noge Ichiro, Higashigawa Masamune, Komada Yoshihiro
Department of Clinical Pharmaceutics, School of Pharmaceutical Sciences, University of Shizuoka; 52-1 Yada, Surugaku, Shizuoka, Shizuoka 422-8526, Japan.
Biol Pharm Bull. 2008 Jan;31(1):57-61. doi: 10.1248/bpb.31.57.
We investigated the combined effect of cyclophosphamide (CPA) and 5-bromo-2'-deoxyuridine (BrdUrd) both in mice bearing L1210 ascites tumors and in L1210 leukemic cells in vitro. Administration of BrdUrd (100 mg/kg) for 5 consecutive days before a single dose (80 mg/kg) of CPA significantly extended the survival of mice by 158%, compared with CPA alone. BrdUrd administered at daily doses of 100 or 200 mg/kg for 5 consecutive days did not extended the survival of mice. An in vitro MTT assay revealed that BrdUrd enhanced the cytotoxic effect of 4-hydroxycyclophosphamide, an active form of CPA, in the L1210 cells. These results indicate that BrdUrd enhanced the antitumor effect of CPA both in vivo and in vitro.
我们研究了环磷酰胺(CPA)和5-溴-2'-脱氧尿苷(BrdUrd)对携带L1210腹水瘤的小鼠以及体外培养的L1210白血病细胞的联合作用。在单次给予CPA(80 mg/kg)前连续5天给予BrdUrd(100 mg/kg),与单独使用CPA相比,显著延长了小鼠的生存期,延长幅度达158%。连续5天每日给予100或200 mg/kg的BrdUrd并未延长小鼠的生存期。体外MTT分析显示,BrdUrd增强了CPA的活性形式4-羟基环磷酰胺对L1210细胞的细胞毒性作用。这些结果表明,BrdUrd在体内和体外均增强了CPA的抗肿瘤作用。