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

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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 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.

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Funding

This work was supported by the Sakarya University Scientific Research Projects Unit [SAU-BAPK] under Grant [Number 2019-6-21-183].

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Authors and Affiliations

  1. Department of Medical Biology, Faculty of Medicine, Sakarya University, Korucuk Campus, 54290, Sakarya, Turkey

    Asuman Deveci Ozkan, Gamze Guney Eskiler & Suleyman Kaleli

  2. Department of Histology and Embryology, Faculty of Medicine, Sakarya University, Sakarya, Turkey

    Elvan Sahin

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  1. Asuman Deveci Ozkan
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  2. Gamze Guney Eskiler
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  3. Suleyman Kaleli
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Contributions

ADO and GGE originated and designed the research. SK and ES advised on experimental design. ADO and GGE conducted experiments. ADO, GGE, SK and ES analyzed and interpreted the data. All authors read carefully and approved the final version of the manuscript to be published.

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Correspondence to Asuman Deveci Ozkan.

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Deveci Ozkan, A., Guney Eskiler, G., Kaleli, S. et al. Immunotherapeutic role of cabazitaxel treatment in the activation of TLR3 signalling in metastatic castration-resistant prostate cancer in vitro. Mol Biol Rep 49, 1261–1271 (2022). https://doi.org/10.1007/s11033-021-06953-2

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  • DOI: https://doi.org/10.1007/s11033-021-06953-2

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