Immunotherapeutic role of cabazitaxel treatment in the activation of TLR3 signalling in metastatic castration-resistant prostate cancer in vitro.
Mol Biol Rep
; 49(2): 1261-1271, 2022 Feb.
Article
em En
| MEDLINE
| ID: mdl-34826050
ABSTRACT
BACKGROUND:
The activation of toll like receptors (TLR) potentially affect the inflammatory tumor microenvironment and thus is associated with tumor growth or inhibition. Cabazitaxel (CAB) has been effectively used for the treatment of metastatic castration-resistant prostate cancer (mCRPC). However, the immune regulatory role of CAB in the tumor microenvironment is not clear. In this context, we for the first time assessed the immunotherapeutic role of CAB in the TLR3 signalling following activation of Poly IC in mCRPC cells. METHODS ANDRESULTS:
The cytotoxic and apoptotic effects of CAB with the induction of Poly IC were determined by WST-1, Annexin V, acridine orange, RT-PCR analysis, ELISA assay and immunofluorescence staining in DU-145 mCRPC and HUVEC control cells. Our findings showed that CAB treatment with Poly IC significantly suppressed the proliferation of DU-145 cells through the induction of apoptosis and caspase activation. Additionally, higher concentration of CAB mediated the activation of TLR3 via increased cytoplasmic and nuclear expression of TLR3, TICAM-1 and IRF-3 in mCRPC cells.CONCLUSIONS:
Co-treatment of CAB and Poly IC was more effective in mCRPC cells with less toxicity in control cells. However, further investigations are required to elucidate the molecular mechanisms of TLRs signalling upon CAB treatment at the molecular level to further validate the immunotherapeutic efficacy of CAB in mCRPC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Taxoides
/
Receptor 3 Toll-Like
/
Neoplasias de Próstata Resistentes à Castração
Limite:
Humans
/
Male
Idioma:
En
Revista:
Mol Biol Rep
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Turquia