Enhanced antitumour effect of photodynamic therapy by microtubule inhibitors.

The combination of photodynamic therapy (PDT) and the microtubule (MT) inhibitor, vincristine (VCR) or taxol, was studied in the CaD2 mammary tumour model in mice. Meso-tetra(di-adjacent-sulphonatophenyl) porphine (TPPS2a) was used as a photosensitizer. An enhanced antitumour effect was found when VCR, at an almost non-toxic dose (1 mg/kg1, was injected i.p. into the mice 6 h before PDT, while no such enhanced effect was observed when the same dose of VCR was given either 12 or 24 h before PDT or immediately before PDT. Furthermore, it was found that the number of mitotic cells increased 4-5-fold 6 h after the injection of VCR into the mice. VCR did not enhance the sensitivity of normal skin to PDT. Combination of PDT and taxol was also studied. The antitumour activity of PDT could be increased by taxol when the drug (35 mg/kg) was administered i.p. either 6 h prior to PDT or immediately after or before PDT. No significant enhancement in PDT efficiency was found when PDT with photofrin was combined with VCR.