Elimination of Enhanced Thermal Resistance of Spheroid Culture Model of Prostate Carcinoma Cell Line by Inhibitors of Hsp70 Induction

The purpose of this study was to investigate the enhanced thermal resistance mechanism of the DU145 tumor spheroid cultures as compared to the prostate carcinoma cell line's monolayer cultures. DU145 cells were cultured either as spheroids or monolayers. Cultures were treated with hyperthermia in a precision water bath (at 43°C for 60 minutes) and/or quercetin (50 and 500 μM for monolayer and spheroid cultures respectively). After hyperthermic treatment, the cell viability colony forming ability, and the expression of heat shock protein 70 (Hsp70) were examined in both culture systems. Hsp70 expression was studied using the western blot method. Our results showed that the DU145 monolayer and spheroid cell culture treatment with hyperthermia alone resulted in a marked survival inhibition. Furthermore, the spheroids showed a more significant resistance to hyperthermia compared to the monolayer cultures (p = 0.01). They also produced more Hsp70 than the monolayer cultures. Treatment of cells with quercetin reduced the Hsp70 level in both culture systems. However, with the reduced Hsp70 levels, thermal resistance of the spheroids showed a greater decrease in relation to that of the monolayers. The results suggest that the enhanced hyperthermia resistance mechanism of the spheroid cultures compared to that of the monolayer cultures can be attributed to spheroid's Hsp70 production.