Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1007/s12672-018-0323-z http://hdl.handle.net/11449/179524 |
Resumo: | Use of drug combinations that target different pathways involved in the development and progression of prostate cancer (PCa) has emerged as an alternative to overcome the resistance caused by drug monotherapies. The antiandrogen abiraterone acetate and the PI3K/Akt inhibitor NVP-BEZ235 (BEZ235) may be suitable options for the prevention of drug resistance and the inhibition of PCa progression. The aim of the present study was to evaluate whether abiraterone acetate and BEZ235 achieve superior therapeutic effects to either drug administered as monotherapy, in the early stages of PCa in an androgen-dependent system. Our study showed that each drug might impair tumor growth by reducing proliferation and increasing cell death when administered as monotherapy. However, tumor growth continued to progress with each drug monotherapy and some important side effects were related to BEZ. Conversely, when used in combination, the drugs impaired the inflammatory response, decreased hyperplastic lesions, and blocked tumor progression from premalignant to a malignant stage. Our data showed that the strategy to block the androgenic and PI3K/AKT/mTOR pathway is an effective therapeutic option and should be investigated including distinct PI3K pathway inhibitors. |
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Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in RatsUse of drug combinations that target different pathways involved in the development and progression of prostate cancer (PCa) has emerged as an alternative to overcome the resistance caused by drug monotherapies. The antiandrogen abiraterone acetate and the PI3K/Akt inhibitor NVP-BEZ235 (BEZ235) may be suitable options for the prevention of drug resistance and the inhibition of PCa progression. The aim of the present study was to evaluate whether abiraterone acetate and BEZ235 achieve superior therapeutic effects to either drug administered as monotherapy, in the early stages of PCa in an androgen-dependent system. Our study showed that each drug might impair tumor growth by reducing proliferation and increasing cell death when administered as monotherapy. However, tumor growth continued to progress with each drug monotherapy and some important side effects were related to BEZ. Conversely, when used in combination, the drugs impaired the inflammatory response, decreased hyperplastic lesions, and blocked tumor progression from premalignant to a malignant stage. Our data showed that the strategy to block the androgenic and PI3K/AKT/mTOR pathway is an effective therapeutic option and should be investigated including distinct PI3K pathway inhibitors.Department of Morphology Institute of Biosciences Sao Paulo State University (UNESP), Rua Professor Doutor Antonio Celso Wagner Zanin, 250Institute of Biosciences Humanities and Exact Sciences Sao Paulo State University (UNESP)Institute of Biology University of Campinas (UNICAMP)Department of Morphology Institute of Biosciences Sao Paulo State University (UNESP), Rua Professor Doutor Antonio Celso Wagner Zanin, 250Institute of Biosciences Humanities and Exact Sciences Sao Paulo State University (UNESP)Universidade Estadual Paulista (Unesp)Universidade Estadual de Campinas (UNICAMP)Gonçalves, Bianca Facchim [UNESP]de Campos, Silvana Gisele Pegorin [UNESP]Fávaro, Wagner JoséBrandt, Joyce Zalotti [UNESP]Pinho, Cristiane Figueiredo [UNESP]Justulin, Luis Antônio [UNESP]Taboga, Sebastião Roberto [UNESP]Scarano, Wellerson Rodrigo [UNESP]2018-12-11T17:35:31Z2018-12-11T17:35:31Z2018-01-23info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article1-13application/pdfhttp://dx.doi.org/10.1007/s12672-018-0323-zHormones and Cancer, p. 1-13.1868-85001868-8497http://hdl.handle.net/11449/17952410.1007/s12672-018-0323-z2-s2.0-850408684302-s2.0-85040868430.pdfScopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengHormones and Cancer1,2511,251info:eu-repo/semantics/openAccess2023-12-04T06:13:33Zoai:repositorio.unesp.br:11449/179524Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462023-12-04T06:13:33Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats |
title |
Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats |
spellingShingle |
Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats Gonçalves, Bianca Facchim [UNESP] |
title_short |
Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats |
title_full |
Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats |
title_fullStr |
Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats |
title_full_unstemmed |
Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats |
title_sort |
Combinatorial Effect of Abiraterone Acetate and NVP-BEZ235 on Prostate Tumor Progression in Rats |
author |
Gonçalves, Bianca Facchim [UNESP] |
author_facet |
Gonçalves, Bianca Facchim [UNESP] de Campos, Silvana Gisele Pegorin [UNESP] Fávaro, Wagner José Brandt, Joyce Zalotti [UNESP] Pinho, Cristiane Figueiredo [UNESP] Justulin, Luis Antônio [UNESP] Taboga, Sebastião Roberto [UNESP] Scarano, Wellerson Rodrigo [UNESP] |
author_role |
author |
author2 |
de Campos, Silvana Gisele Pegorin [UNESP] Fávaro, Wagner José Brandt, Joyce Zalotti [UNESP] Pinho, Cristiane Figueiredo [UNESP] Justulin, Luis Antônio [UNESP] Taboga, Sebastião Roberto [UNESP] Scarano, Wellerson Rodrigo [UNESP] |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade Estadual Paulista (Unesp) Universidade Estadual de Campinas (UNICAMP) |
dc.contributor.author.fl_str_mv |
Gonçalves, Bianca Facchim [UNESP] de Campos, Silvana Gisele Pegorin [UNESP] Fávaro, Wagner José Brandt, Joyce Zalotti [UNESP] Pinho, Cristiane Figueiredo [UNESP] Justulin, Luis Antônio [UNESP] Taboga, Sebastião Roberto [UNESP] Scarano, Wellerson Rodrigo [UNESP] |
description |
Use of drug combinations that target different pathways involved in the development and progression of prostate cancer (PCa) has emerged as an alternative to overcome the resistance caused by drug monotherapies. The antiandrogen abiraterone acetate and the PI3K/Akt inhibitor NVP-BEZ235 (BEZ235) may be suitable options for the prevention of drug resistance and the inhibition of PCa progression. The aim of the present study was to evaluate whether abiraterone acetate and BEZ235 achieve superior therapeutic effects to either drug administered as monotherapy, in the early stages of PCa in an androgen-dependent system. Our study showed that each drug might impair tumor growth by reducing proliferation and increasing cell death when administered as monotherapy. However, tumor growth continued to progress with each drug monotherapy and some important side effects were related to BEZ. Conversely, when used in combination, the drugs impaired the inflammatory response, decreased hyperplastic lesions, and blocked tumor progression from premalignant to a malignant stage. Our data showed that the strategy to block the androgenic and PI3K/AKT/mTOR pathway is an effective therapeutic option and should be investigated including distinct PI3K pathway inhibitors. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-12-11T17:35:31Z 2018-12-11T17:35:31Z 2018-01-23 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1007/s12672-018-0323-z Hormones and Cancer, p. 1-13. 1868-8500 1868-8497 http://hdl.handle.net/11449/179524 10.1007/s12672-018-0323-z 2-s2.0-85040868430 2-s2.0-85040868430.pdf |
url |
http://dx.doi.org/10.1007/s12672-018-0323-z http://hdl.handle.net/11449/179524 |
identifier_str_mv |
Hormones and Cancer, p. 1-13. 1868-8500 1868-8497 10.1007/s12672-018-0323-z 2-s2.0-85040868430 2-s2.0-85040868430.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Hormones and Cancer 1,251 1,251 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
1-13 application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
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1799965168162045952 |