Photodynamic therapy with photofrin in combination with Buthionine Sulfoximine (BSO) of human glioma in the nude rat.
High concentrations of cellular glutathione (GSH) within tumour cells may reduce the ability of photodynamic therapy (PDT) to selectively destroy tumour, consequently, a means of improving the therapeutic ratio of PDT in brain tumour is necessary. Therefore, we hypothesize that PDT in combination with Buthionine Sulfoximine (BSO), an agent which lowers cellular glutathione, can significantly enhance destruction of U87 and U251n tumour cells. PDT was performed using Photofrin as a photosensitiser in combination with BSO administration on male Fisher rats with intracerebral U87 and on non-tumour rats (administered at different optical doses in combination with Photofrin). In vitro experimentation utilising colony forming, cell cytotoxicity, and matrigel artificial basement membrane invasion assays showed significant enhancement of tumour kill and significant reduction of migration in tumour cells treated with BSO in combination with Photofrin PDT in comparison with individual therapies for both U87 and U251n cell lines. In vivo combination PDT-BSO treatment of U87 tumour rats exhibited significantly more tumour necrosis than individual treatments. In conclusion, our data suggests BSO enhances Photofrin PDT treatment of human glioma.
D000818:Animals; D019328:Buthionine Sulfoximine / Q000008:administration & dosage*; D017323:Dihematoporphyrin Ether / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D005978:Glutathione / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008297:Male; D010778:Photochemotherapy; D017319:Photosensitizing Agents; D051381:Rats; D011923:Rats, Nude; D014407:Tumor Cells, Cultured
D017319:Photosensitizing Agents; D019328:Buthionine Sulfoximine; D017323:Dihematoporphyrin Ether; D005978:Glutathione