Unique synergism or antagonism of combinations of chemotherapeutic and hormonal agents in human prostate cancer cell lines

Objective To evaluate combinations of anti-tumour agents in tissue cultures using three established cell lines derived from patients with prostate cancer to obtain potential candidates for therapeutic testing in patients with prostate cancer. Materials and methods Seventeen anti-tumour agents were tested for synergism or antagonism in combination studies in DU 145, PC 3 and LnCaP cell lines. After determining the dose required for 50% inhibition of growth in each, combinations were screened using the median-effect plot and combination-index isobolograms. Results Estramustine (the primary product of dephosphorylation of estramustine phosphate) showed strong synergism in all three cell lines with hydroxyflutamide, the non-immunosuppressive cyclosporin analogue PSC 833, and Liarozole . In the hormone-sensitive cell line LnCaP alone, synergism was also observed with vinblastine, paclitaxel, docetaxel, bicalutamide, ketoconazole and all-trans-retinoic acid. Other synergistic combinations of two agents were: Liarozole plus docetaxel in LnCaP, PSC 833 plus bicalutamide in DU 145 and PC 3, dexamethasone plus docetaxel in LnCaP, and finasteride plus hydroxyflutamide. Synergistic combinations of three agents were: estramustine plus PSC 833 and Liarozole and schedule-dependent combinations of estramustine, PSC 833, and all-trans-retinoic acid. Conclusion Some of the synergistic combinations have shown clinical effects in patients with hormone-refractory prostate cancer. Based on these findings, new combinations, e.g. estramustine with either PSC 833 or Liarozole, need to be clinically evaluated.