Response of PC-3 prostate cancer cells to combination therapy using irradiation with glucocorticoids or doxorubicin.
OBJECTIVE
We evaluated the effects of irradiation, doxorubicin and dexamethasone on human PC-3 prostate cancer cells, investigating whether dexamethasone and doxorubicin can alter the irradiation cytotoxicity of PC-3 cells.


METHODS
We used the human PC-3 prostate cancer cells, analyzing cell growth with trypan blue exclusion, indices of the cell cycle with flow cytometry and apoptosis with flow cytometry and analysis of DNA fragmentation on simple 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, exerting an inhibitory effect on the proliferation of PC-3 cells after 48 and 72 hr, but it did not produce apoptosis. Irradiation (4 Gy) initially arrested cells at the G2/M phase in the cell cycle (24 hr) which was gradually overcome and the PC-3 cells were shifted into G0/G1 phase or apoptosis after 48 and 72 hr. Irradiation decreased the PC-3 cell growth by 40-50% after 48 and 72 hr, respectively. Treatment with doxorubicin (100 nM) for 24, 48, and 72 hr after irradiation potentiated irradiation cytotoxicity of PC-3 cells. Dexamethasone treatment 24 hr before and 24, 48 and 72 hr after irradiation increased the number of surviving PC-3 cells and partially neutralized the irradiation effects on cell cycle.


CONCLUSIONS
Doxorubicin potentiated while dexamethasone partially reversed the irradiation cytotoxicity of PC-3 cells. These data may be of clinical importance for the treatment of hormone refractory prostate cancer.
Kruit
A
A
Molecular Endocrinology, Research Center, Centre Hospitalier Universitaire de Quebec (CHUQ), Laval University, Ste. Foy, Canada.
Reyes-Moreno
C
C
Newling
D W
DW
Geldof
A
A
Koutsilieris
M
M
D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D003907:Dexamethasone / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D005720:Gamma Rays; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D003907:Dexamethasone; D004317:Doxorubicin