Immunotherapeutic role of cabazitaxel treatment in the activation of TLR3 signalling in metastatic castration-resistant prostate cancer in vitro

• Published in: Molecular biology reports Vol. 49; no. 2; pp. 1261 - 1271
• Main Authors: Deveci Ozkan, Asuman, Guney Eskiler, Gamze, Kaleli, Suleyman, Sahin, Elvan
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2022; Springer Nature B.V
• Subjects: Acridine orange; Animal Anatomy; Animal Biochemistry; Annexin V; Antineoplastic Agents - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Caspase; Castration; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cytotoxicity; Docetaxel - pharmacology; Enzyme-linked immunosorbent assay; Histology; Humans; Immunofluorescence; Immunotherapy - methods; Inflammation; Interferon Regulatory Factor-3; Life Sciences; Male; Metastases; Metastasis; Molecular modelling; Morphology; Neoplasm Metastasis - genetics; Original Article; Poly (I:C); Polymerase chain reaction; Prostate cancer; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - immunology; Prostatic Neoplasms, Castration-Resistant - metabolism; Signal Transduction - drug effects; Taxoids - immunology; Taxoids - metabolism; Taxoids - pharmacology; TLR3 protein; Toll-Like Receptor 3 - drug effects; Toll-Like Receptor 3 - metabolism; Toll-like receptors; Tumor microenvironment; Tumor Microenvironment - drug effects; Tumors; Toll like receptor 3; Taxanes; Cabazitaxel; Toll like receptors; Apoptosis
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-021-06953-2

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 I:C in mCRPC cells. Methods and results The cytotoxic and apoptotic effects of CAB with the induction of Poly I:C 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 I:C 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 I:C 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.