Abstract

Background: The propagation of injury ("bystander effect") from directlydamaged cells to other cells has been observed in cancer therapies. Some experiments suggested that thisphenomenon was also detected in photodynamic therapy (PDT). The present study was undertaken to evaluatethe bystander response in cells co-cultured with PDT- or heat-injured cells. Material/Methods: Humanovary cancer cells (OVP10) were co-cultivated with PDT- and heat-damaged cells under various conditions.Fluorescence and light microscopy, shear test, clonogenic assays, and RT-PCR were used to estimate thevital functions of intact cells. Results: In the shear test, the addition of damaged cells to a monolayerof uninjured OVP10 cells resulted in a significant cell detachment of up to 87% for PDT-treated cellsand 74% for heat-treated cells. Cells that were co-cultured with their PDT-injured counterparts in aproportion of 50% showed progressive decreases in density by 7% and 38% (significant) after 24 and 48h, respectively. In co-culture with heat-damaged cells, the density decreased significantly by 21% and28% after 24 and 48 h. "Bystander" growth arrest is attributed to a significant decrease in mitotic activityat 24 h and a lower expression of the focal adhesion kinase gene (FAK). Neither PDT- nor heat-damagedcells induced changes in mRNA expressions for GADD45, P21(WAF/cip1), C-JUN, C-FOS, and BAX in the bystandercells. Conclusions: Bystander response may modulate the growth and adhesion of cells co-cultured withtheir PDT- and heat-injured counterparts in vitro.

Keywords: Cell Adhesion, Base Sequence, Cell Division, Coculture Techniques, Gene Expression, Hyperthermia, Induced, Mitosis, Models, Biological, Ovarian Neoplasms - therapy, Photochemotherapy, RNA, Messenger - metabolism, RNA, Neoplasm - metabolism