Chemosensitizing Effect and Efficacy of Wilforlide A in Combination With Docetaxel in Drug-resistant Prostate Cancer.
In Vivo
; 36(5): 2020-2031, 2022.
Article
em En
| MEDLINE
| ID: mdl-36099129
ABSTRACT
BACKGROUND/AIM:
Prostate cancer is currently the second most common cancer in men and chemotherapy is the main treatment for metastatic castrate-resistant prostate cancers (mCRPC). However, chemoresistance leading to treatment failure is inevitable. Thus, therapeutic approaches that can overcome chemoresistance are important areas of research for cancer chemotherapy. MATERIALS ANDMETHODS:
In the present study, six components of tripterygium wilfordii including celastrol, triptolide, pristimerin, triptonide, demethylzeylasteral, and wilforlide A were screened for their chemosensitizing effect on drug-resistant prostate cancer cell lines PC3 and DU145. The most active compound was further investigated on its potential mechanism of action and in vivo efficacy using a SCID mouse model.RESULTS:
Among the six components only wilforlide A significantly enhanced sensitivity to docetaxel (by reducing the IC50 in resistant prostate cancer cell lines). Wilforlide A inhibited P-glycoprotein efflux transporter and downregulated cyclin E2 splice variant 1 mRNA, both have been known as mechanisms of resistance. The chemosensitizing effect was further verified using a xenograft mouse model. In the high-dose treatment group, the combination of wilforlide A and docetaxel significantly retarded tumor growth of resistant prostate cancer, although neither docetaxel nor wilforlide A monotreatment groups showed any effect.CONCLUSION:
Wilforlide A was found to enhance the chemosensitizing effect of docetaxel both in vitro and in vivo. Further studies are warranted to verify wilforlide A as a new drug candidate to overcome docetaxel resistance in prostate cancer.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Taxoides
/
Neoplasias de Próstata Resistentes à Castração
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
In Vivo
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2022
Tipo de documento:
Article