PAK1 inhibitor IPA-3 mitigates metastatic prostate cancer-induced bone remodeling.
Biochem Pharmacol
; 177: 113943, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32240651
ABSTRACT
Metastatic prostate cancer (PCa) has high mortality and a poor 5-year survival rate primarily due to the lack of effective treatments. Bone is the primary site of PCa metastasis in humans and the development of reliable therapeutic options for bone metastatic PCa will make a huge impact in reducing the mortality among these patients. Although P21 activated kinases (PAKs) have been studied in the past for their role in cancer, the efficacy of targeting PAKs to treat lung and bone metastatic PCa has not been tested yet. In the current study, we report that targeting PAK1 using IPA-3, an allosteric inhibitor of PAK1 kinase activity, significantly inhibits the murine metastatic PCa (RM1) cell proliferation and motility in vitro, and metastasis to the lungs in vivo. More importantly, we demonstrate for the first time that treatment with IPA-3 can blunt metastatic PCa-induced bone remodeling in vivo as analyzed by the 3-dimensional microcomputer tomography analysis. Our study has identified IPA-3 as a potential drug to treat bone metastatic PCa.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Próstata
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Remodelação Óssea
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Dissulfetos
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Quinases Ativadas por p21
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Neoplasias Pulmonares
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Naftóis
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
2020
Tipo de documento:
Article