Resistance to Photodynamic Therapy induced by trnasfection of the H-Ras oncogen

RODRIGUEZ L, CASAS A, DI VENOSA G, SCHICKINGER, MACROBERT, BATLLE A.

Bressanone, Italia

Congreso; Photodynamic Therapy and Photodiagnosis in Clinical Practice; 2008

Photodynamic therapy (PDT) is a treatment modality available for palliation or eradication of several cancers. PDT involves the systemic or topical administration of a tumour-localising photoactive drug or photosensitiser (PS), and its subsequent activation by visible light (typically visible or infrared) to result primarily in singlet oxygen-induced photodamage to the tumour. The aim of this work was to compare various photosensitisers (Photofrin, Verteporfin, Merocyanine 540, Acridine Orange and Foscan) accumulation and intracellular localisation in a normal/tumour cell line pair, and to establish a correlation with the response to PDT. We employed the normal mammary luminal epithelial HB4a and its tumour counterpart transfected with the oncogene H-Ras /VAL/12Ras).Optimal conditions of time exposure and concentrations were settled for every PS. It was found that Lethal Doses 50 for PDT were: Verteporphyrin: HB4a: 1±0.1 min, HB4a-Ras: 2±0.2 min (p=0,001); Acridin Orange: HB4a:3± 0.2 min, HB4a-Ras: 4.2±0.5 min (p=0.004); Foscan, HB4a: 4.3±0.5 min, HB4a-Ras: 4.6±0.3 min (not significantly different.);  Photofrin, HB4a: 4.6±0.4 min, HB4a-Ras: 7.8±0.8 min (p=0,004) and Merocyanin 540, HB4a: 15±1.8 min, HB4a-Ras: 21.5±2 min (p=0,003). The results demonstrate that Ras-transfected cells are more resistant than normal cells to PDT with all the PSs except for Foscan.  We believe that survival signals are involved in the process.