Novel treatment modalities are urgently required for
androgen-independent
prostate cancer. In order to develop an alternative treatment for
prostate cancer, the cytotoxic effects of the
26S proteasome inhibitor
bortezomib, either alone or in combination with the two commonly used chemotherapeutic agents
irinotecan and
etoposide, on the human
prostate cancer cell line PC-3 were evaluated in the present study. The PC-3 cell line was maintained in Dulbecco's modified Eagle's medium with 10%
fetal bovine serum and treated with various doses of
bortezomib,
irinotecan,
etoposide or their combinations. The growth inhibitory and cytotoxic effects were determined by water-soluble tetrazolium (WST)-1 assay,
3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay or iCELLigence system. The combination index values were determined by the Chou-Talalay method. The half maximal inhibitory concentration (IC50) value of
bortezomib on the PC-3 cell line was determined to be 53.4 nM by WST-1 assay, whereas the IC50 values of
irinotecan and
etoposide were determined to be 2.1 and 26.5 µM, respectively. These results suggest that the
26S proteasome inhibitor
bortezomib is more potent, compared with
irinotecan and
etoposide, in the
androgen-insensitive and
tumor protein p53-null cell line PC-3. The combined effects of bortezomib+irinotecan and bortezomib+etoposide were also tested on PC-3 cells. The effect of bortezomib+irinotecan combination was not significantly different than that produced by either monotherapy, according to the results of iCELLigence system and MTT assay. However, 40 nM bortezomib+5 µM
etoposide or 40 nM bortezomib+20 µM
etoposide combinations were observed to be more effective than each
drug tested alone. The results of the current study suggest that
bortezomib and
etoposide combination may be additionally evaluated in clinical trials for the treatment of
hormone-refractory
prostate cancer.