Ma L W, Moan J, Steen H B, Iani V
Department of Biophysics, Institute of Cancer Research, Montebello, Oslo, Norway.
Br J Cancer. 1995 May;71(5):950-6. doi: 10.1038/bjc.1995.184.
The interaction of photodynamic therapy (PDT) and a chemotherapeutic drug, mitomycin C (MMC), was investigated using WiDr human colon adenocarcinoma tumours implanted on Balb/c athymic nude mice. The WiDr tumours were treated with PDT alone, MMC alone or with both. It was found that the combined treatment produced a greater retardation in the growth of the WiDr tumour than monotherapy with MMC or PDT. The synergistic effect was especially prominent when PDT was used in combination with a low dose of MMC (1 mg kg-1), since treatment of 1 mg kg-1 MMC alone had no effect on the tumour. The anti-tumour activity of PDT was found to be increased with MMC of 5 mg kg-1. The response of normal skin on mice feet to PDT slightly greater when PDT was combined with 5 mg kg-1 MMC than when PDT was applied alone, while no detectable additional effect on skin photosensitivity was observed when PDT was combined with 1 mg kg-1 MMC. An enhanced uptake of Photofrin in tumours was found 12 h and 24 h after administration of MMC. The effect of MMC on the cell cycle distribution of cell dissociated directly from the tumours was studied. The results suggest that the increased susceptibility to photoinactivation of Photofrin-sensitised tumours may be due to MMC-induced accumulation of the tumour cells in S-phase.
利用接种于Balb/c无胸腺裸鼠的WiDr人结肠腺癌肿瘤,研究了光动力疗法(PDT)与化疗药物丝裂霉素C(MMC)的相互作用。对WiDr肿瘤分别单独进行PDT治疗、单独进行MMC治疗或两者联合治疗。结果发现,联合治疗比单独使用MMC或PDT的单一疗法对WiDr肿瘤的生长有更大的抑制作用。当PDT与低剂量MMC(1mg/kg)联合使用时,协同效应尤为显著,因为单独使用1mg/kg的MMC对肿瘤没有作用。发现5mg/kg的MMC可增强PDT的抗肿瘤活性。当PDT与5mg/kg的MMC联合使用时,小鼠足部正常皮肤对PDT的反应比单独应用PDT时略大,而当PDT与1mg/kg的MMC联合使用时,未观察到对皮肤光敏性有可检测到的额外影响。在给予MMC后12小时和24小时,发现肿瘤中Photofrin的摄取增加。研究了MMC对直接从肿瘤中解离的细胞的细胞周期分布的影响。结果表明,Photofrin致敏肿瘤对光灭活的敏感性增加可能是由于MMC诱导肿瘤细胞在S期积累所致。