Induction of Hsp60 by photofrin-mediated photodynamic therapy

Photodynamic therapy (PDT) invokes a number of cellular responses. Other st udies have shown that PDT induces transcription and translation of heat sho ck proteins (Hsps). The expression of mitochondrial heat shock protein, Hsp 60, was measured following in vitro Photofrin-mediated PDT in the colon can cer cell line HT29 and its PDT-induced resistant variant HT29-P14 as well a s the radiation-induced fibrosarcoma cells RIF-I and its PDT-induced resist ant variant, RIF-8A. Basal levels of Hsp60 were found to be similar in the two murine cell lines. In the human model, the resistant HT29-P14 cell line showed a small increase in basal levels relative to its parental populatio n. Incubation with Photofrin (R) (PH) alone or photosensitization caused a significant increase in Hsp60 levels in all cell lines as determined by flo w cytometry. A dose-dependent and temporal relationship for PDT response wa s observed, maximum levels were detected 6-8 h post PDT, at which time, Hsp 60 induction was found to be significantly greater in the two resistant var iants. Induction in the RIF cells was also found to be greater after incuba tion with PH alone at the highest doses tested. These results indicate that the presence of PH and the subsequent oxidative stress of PDT can induce H sp60 and implicated it as a common factor that may contribute to the resist ance observed in the induced resistant cells. (C) 2001 Elsevier Science B.V . All rights reserved.