Constitutive overexpression of HSP-70 in thermal resistant tumor cells does not alter sensitivity to porphyrin-, chlorin-, or purpurin-mediated PDT

Cellular expression of the 70 kDa heat shock protein (HSP-70) is observed f ollowing hyperthermia and is correlated with transient resistance to subseq uent heating. Photodynamic therapy (PDT) mediated oxidative stress can also induce transcriptional and translational expression of a variety of genes including HSP-70. However, PDT-mediated HSP-70 expression can Vary as a fun ction of photosensitizer type and incubation conditions. In the current stu dy we used three clinically relevant photosensitizers, a porphyrin (Photofr in), a purpurin (SnET2), and a chlorin (NPe6), to examine PDT-mediated HSP- 70 expression profiles and photosensitivity characteristics in parental rad iation-induced fibrosarcoma cells (RIF-1) and in thermal resistant RIF-I cl ones. We observed that in vitro PDT treatments using either SnET2 or NPe6 i nduced HSP-70 expression but that comparable PDT treatments using Photofrin did not result in increased HSP-70 levels. We also observed that PDT sensi tivity in parental and heat-resistant cell clones were similar for each pho tosensitizer while thermal sensitivity was significantly reduced in the RIF clones which constitutively overexpressed HSP-70. These results indicate t hat definable differences can exist in the molecular pathways induced by PD T for different photosensitizers. Our results also demonstrate that constit utive overexpression of HSP-70 does not modulate PDT photosensitivity regar dless of whether PDT treatments induce HSP-70 expression. We conclude that HSP-70 expression does not play a significant role in cellular PDT photosen sitivity, Copyright (C) 2001 John Wiley & Sons, Ltd.