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

✍ Scribed by Natalie Rucker; Angela Ferrario; Charles J. Gomer

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 114 KB
• Volume: 05
• Category: Article
• ISSN: 1088-4246
• DOI: 10.1002/jpp.322

✦ Synopsis

Cellular expression of the 70 kDa heat shock protein (HSP-70) is observed following hyperthermia and is correlated with transient resistance to subsequent 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 function of photosensitizer type and incubation conditions. In the current study we used three clinically relevant photosensitizers, a porphyrin (Photofrin), a purpurin (SnET2), and a chlorin (NPe6), to examine PDT-mediated HSP-70 expression profiles and photosensitivity characteristics in parental radiation-induced fibrosarcoma cells (RIF-1) and in thermal resistant RIF-1 clones. We observed that in vitro PDT treatments using either SnET2 or NPe6 induced HSP-70 expression but that comparable PDT treatments using Photofrin did not result in increased HSP-70 levels. We also observed that PDT sensitivity in parental and heat-resistant cell clones were similar for each photosensitizer while thermal sensitivity was significantly reduced in the RIF clones which constitutively overexpressed HSP-70. These results indicate that definable differences can exist in the molecular pathways induced by PDT for different photosensitizers. Our results also demonstrate that constitutive overexpression of HSP-70 does not modulate PDT photosensitivity regardless of whether PDT treatments induce HSP-70 expression. We conclude that HSP-70 expression does not play a significant role in cellular PDT photosensitivity.