Abstract
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.
Highlights
In the last decade, it has been demonstrated that photodynamic therapy (PDT) can be used for the treatment of many forms of cancer (Dougherty et al, 1990; Henderson, 1990)
S_ry 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 results suggest that the increased susceptibility to photoinactivation of Photofrinsensitised tumours may be due to MMC-induced accumulation of the tumour cells in S-phase
Summary
951 rate at the position of the tumour was measured with a Female Balb/c athymic nude mice were purchased from Bomholt Gaard, Ry, Denmark. 5 x 106 WiDr cells (a human colon adenocarcinoma cell line) suspended in 0.04 ml of phosphate-buffered saline (PBS) were implanted subcutanously on the dorsal side of the foot of the right hind limb of each mouse. At this site the tumour was accessible to treatment and to assessment of response. The mice were assessed regularly and the tumour size was measured along three orthogonal diameters (Dl, D2, D3), every second day using a caliper.
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