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Pretreatment of prostate cancer cells with salinomycin and Wnt inhibitor increases the efficacy of cabazitaxel by inducing apoptosis and decreasing cancer stem cells

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Abstract

Cancer stem cells (CSCs) are associated with metastasis and recurrence in prostate cancer as well as other cancers. We aimed to enhance the sensitivity of cabazitaxel in prostate cancer cell therapy by targeting CSCs with a Wnt inhibitor and salinomycin pretreatment. PC3, DU-145, and LNCaP human prostate cancer cells were exposed to Wnt/β-catenin pathway inhibitor CCT036477 (iWnt) with salinomycin for 48 h, followed by cabazitaxel treatment for 48 h. Cell viability, mRNA, and protein expression changes were evaluated by MTT, RT-qPCR, and Western blot assays, respectively. Apoptosis was determined by image-based cytometry, and cell migration was assessed by wound healing assay. Three-dimensional culture was established to assess the malignant phenotype and stemness potential of transformed or cancer cells. CD44 + CSCs were isolated using magnetic-activated cell sorting system. Pretreatment of PC3, DU-145, and LNCaP cells with salinomycin iWnt significantly sensitized the cells to cabazitaxel therapy. Spheroid culture confirmed that the treatment modality was more effective than a single administration of chemotherapy. The pretreatment of PC3 cells increased the rate of apoptosis compared to single administration of cabazitaxel, which downregulated Bcl-2 and upregulated caspase 3, caspase 8 expressions. The pretreatment suppressed cell migration, downregulated the expression of Sox2 and Nanog, and significantly reduced CD44 + CSC numbers. Notably, the treatment modality reduced pAKT, p-P38 MAPK, and pERK1/2. The data suggest that pretreatment of prostate cancer cells with salinomycin and Wnt inhibitor may increase the efficacy of cabazitaxel therapy by inhibiting cell proliferation and migration, and eliminating cancer stem cells.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Drs. Ruveyde Garip and Sultan Kaya (Trakya University, School of Medicine, Department of Ophthalmology) for their support in the preparation of bovine retinal pigment epithelial cells.

Funding

This study was funded by the Trakya University Research Project Foundation (Project no: 2020-01), Edirne, Turkey.

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  1. Department of Medical Biology, School of Medicine, Trakya University, Balkan Campus, 22030, Edirne, Turkey

    Riza Serttas & Suat Erdogan

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  1. Riza Serttas
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  2. Suat Erdogan
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All authors contributed to the study conception and design. Experiments were performed and analyzed by Riza Serttas. The first draft of the manuscript was written by Suat Erdogan and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Suat Erdogan.

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Serttas, R., Erdogan, S. Pretreatment of prostate cancer cells with salinomycin and Wnt inhibitor increases the efficacy of cabazitaxel by inducing apoptosis and decreasing cancer stem cells. Med Oncol 40, 194 (2023). https://doi.org/10.1007/s12032-023-02062-1

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