The effect of finasteride and dutasteride on the growth of WPE1-NA22 prostate cancer xenografts in nude mice

dc.citation.doi10.1371/journal.pone.0029068en_US
dc.citation.issue1en_US
dc.citation.jtitlePLoS ONEen_US
dc.citation.spagee29068en_US
dc.citation.volume7en_US
dc.contributor.authorOpoku-Acheampong, Alexander B.
dc.contributor.authorNelsen, Michelle K.
dc.contributor.authorUnis, Dave
dc.contributor.authorLindshield, Brian L.
dc.contributor.authoreidblindshen_US
dc.contributor.authoreidalexachen_US
dc.contributor.authoreiddaveunisen_US
dc.date.accessioned2012-02-02T19:30:45Z
dc.date.available2012-02-02T19:30:45Z
dc.date.issued2012-01-05
dc.date.published2012en_US
dc.description.abstractBackground: 5 alpha-reductase 1 (5alphaR1) and 5alpha-reductase 2 (5alphaR2) convert testosterone into the more potent androgen dihydrotestosterone. 5alphaR2 is the main isoenzyme in normal prostate tissue; however, most prostate tumors have increased 5alphaR1 and decreased 5alphaR2 expression. Previously, finasteride (5alphaR2 inhibitor) treatment begun 3 weeks post-tumor implantation had no effect on Dunning R3327-H rat prostate tumor growth. We believe the tumor compensated for finasteride treatment by increasing tumor 5alphaR1 expression or activity. We hypothesize that finasteride treatment would not significantly alter tumor growth even if begun before tumor implantation, whereas dutasteride (5alphaR1 and 5alphaR2 inhibitor) treatment would decrease tumor growth regardless of whether treatment was initiated before or after tumor implantation. Methodology/Principal Findings: Sixty 8-week-old male nude mice were randomized to Control, Pre- and Post-Finasteride, and Pre- and Post-Dutasteride (83.3 mg drug/kg diet) diet groups. Pre- and post-groups began their treatment diets 1–2 weeks prior to or 3 weeks after subcutaneous injection of 1x10[5th power] WPE1-NA22 human prostate cancer cells, respectively. Tumors were allowed to grow for 22 weeks; tumor areas, body weights, and food intakes were measured weekly. At study’s conclusion, prostate and seminal vesicle weights were significantly decreased in all treatment groups versus the control; dutasteride intake significantly decreased seminal vesicle weights compared to finasteride intake. No differences were measured in final tumor areas or tumor weights between groups, likely due to poor tumor growth. In follow-up studies, proliferation of WPE1-NA22 prostate cancer cells and parent line RWPE-1 prostate epithelial cells were unaltered by treatment with testosterone, dihydrotestosterone, or mibolerone, suggesting that these cell lines are not androgensensitive. Conclusion: The lack of response of WPE1-NA22 prostate cancer cells to androgen treatment may explain the inadequate tumor growth observed. Additional studies are needed to determine whether finasteride and dutasteride are effective in decreasing prostate cancer development/growth.en_US
dc.description.versionArticle: Version of Record
dc.identifier.urihttp://hdl.handle.net/2097/13449
dc.relation.urihttp://doi.org/10.1371/journal.pone.0029068en_US
dc.rights© 2012 Opoku-Acheampong et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.rights.urihttps://creativecommons.org/licenses/by/3.0/us/
dc.subjectProstate canceren_US
dc.subjectFinasterideen_US
dc.subjectDutasterideen_US
dc.subjectWPE-NA22 prostate cancer cellsen_US
dc.titleThe effect of finasteride and dutasteride on the growth of WPE1-NA22 prostate cancer xenografts in nude miceen_US
dc.typeTexten_US

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