Response of PC-3 prostate cancer cells to combination therapy using irradiation with glucocorticoids or doxorubicin

Objectives: We evaluated the effects of irradiation, doxorubicin and dexame thasone on human PC-3 prostate cancer cells, investigating whether dexameth asone and doxorubicin can alter the irradiation cytotoxicity of PC-3 cells. Methods: We used the human PC-3 prostate cancer cells, analyzing cell grow th with trypan blue exclusion, indices of the cell cycle with flow cytometr y and apoptosis with Slow cytometry and analysis of DNA fragmentation on si mple agarose gel. Results: Doxorubicin (100 nM) arrested cell cycle at the G2/M phase, decreased cell growth and produced apoptosis of PC-3 cells in a time-dependent manner Dexamethasone (100 nM) increased the distribution of PC-3 cells at G0/G1 phase in the cell cycle, everting an inhibitory effect on the proliferation of PC-3 cells after. 48 and 72 hr; but it did not pro duce apoptosis. Irradiation(4Gy) initially arrested cells at the G2/M phase in the cell cycle(24 hr) which was gradually overcome and the PC-3 cells w ere shifted into G0/G1 phase or apoptosis after 48 and 72 hr. Irradiation d ecreased the PC-3 cell growth by 40-50% after 48 and 72 hr; respectively. T reatment with doxorubicin(100 nM) for 24, 48 and 72 hl after irradiation po tentiated irradiation cytotoxicity of PC-3 cells. Dexamethasone treatment 2 4 hi before and 24, 48 and 72 hr after irradiation increased the number of surviving PC-3 cells and partially neutralized the irradiation effects on c ell cycle. Conclusion: Doxorubicin potentiated while dexamethasone partiall y reversed the irradiation cytoxicity of PC-3 cells. These data may be of c linical importance for the treatment of hormone refractory prostate cancer.