Prostate epithelial stem cells are resistant to apoptosis after α1-antagonist treatment. The impact for BPH patients

摘要

Introduction. Induction of apoptosis in prostatic epithelialcells by doxazosin, terazosin and prazosin has beenwell documented. However, the biochemical pathways ofdoxazosin action is still unclear. Aforementioned drugsshould lead to decrease of prostate volume, althoughthis effect was never observed in patients suffering fromBPH after treatment with α1-antagonists. Probably,it is connected with cancer stem cells’ resistance onchemotherapeutic agents. The aim of this study was tocompare incidence of apoptosis induced by doxazosin inprogenitor and differentiated cells isolated from humanprostate epithelium.Material and methods. For this purpose tissue specimenswere obtained from 10 patients suffering fromBPH, the primary cultures of prostate epitheliumwere established and CD133 MicroBeads sorting wasprepared. Both, CD133(+)/CD133(-) co-cultures andCD133(+) cells were incubated with different concentrationof doxazosin for 12 h. Cell viability and apoptosiswas estimated with Annexin V-FITC.Results. 12 h incubation of CD133(+)/CD133(-) cocultureswith doxazosin resulted in increase of apoptoticcells, while in CD133(+) cultures no changeswere observed. Correlation between apoptotic cellnumber and doxazosin concentration in CD133(+)/CD133(-) co-cultures group was high (R = 0.99).Conclusion. Doxazosin induced apoptosis in co-culturesof progenitor and differentiated epithelial cells. However,progenitor cells were not susceptible to apoptosis, whatcan be a reason of treatment failure in BPH patients.