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The effect of ciprofloxacin on doxorubicin cytotoxic activity in the acquired resistance to doxorubicin in DU145 prostate carcinoma cells

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Abstract

The present study aimed to assess the influence of ciprofloxacin (CIP) against the doxorubicin (DOX)-resistant androgen-independent prostate cancer DU145 cells. The DOX-resistant DU145 (DU145/DOX20) cells were established by exposing DU145 cells to the increasing concentrations of DOX. The antiproliferative effect of CIP was examined through employing MTT, colony formation, and 3D culture assays. DU145/DOX20 cells exhibited a twofold higher IC50 value for DOX, an increased ABCB1 transporter activity, and some morphological changes accompanied by a decrease in spheroid size, adhesive and migration potential compared to DU145 cells. CIP (5 and 25 µg mL−1) resulted in a higher reduction in the viability of DU145/DOX20 cells than in DU145 cells. DU145/DOX20 cells were more resistant to CIP in 3D culture compared to the 2D one. No spheroid formation was observed for DU145/DOX20 cells treated with DOX and CIP combination. CIP and DOX, alone or in combination, significantly reduced the growth of DU145 spheroids. CIP in combination with 20 nM DOX prevented the colony formation of DU145 cells. The clonogenicity of DU145/DOX20 cells could not be estimated due to their low adhesive potential. CIP alone caused a significant reduction in the migration of DU145 cells and resulted in a more severe decrease in the wound closure ability of DOX-exposed ones. We identified that CIP enhanced DOX sensitivity in DU145 and DU145/DOX20 cells. This study suggested the co-delivery of low concentrations of CIP and DOX may be a promising strategy in treating the DOX-resistant and -sensitive hormone-refractory prostate cancer.

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Acknowledgements

We thank Dr. MR Abbaszadegan and N Taghechian for their kind help with qRT-PCR assay.

Funding

This work was supported by Ferdowsi University of Mashhad, grant number 3/44066. Razieh Jalal has received research support from Ferdowsi University of Mashhad.

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  1. Asieh Davary Avareshk and Jamileh Gholami have contributed equally to this work.

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  1. Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran

    Asieh Davary Avareshk, Razieh Jalal & Jamileh Gholami

  2. Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran

    Razieh Jalal

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RJ: Designed and conducted the experiments, analyzed the data, and wrote the manuscript. ADA and JG: Performed cell biological experiments and analyzed the data.

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Davary Avareshk, A., Jalal, R. & Gholami, J. The effect of ciprofloxacin on doxorubicin cytotoxic activity in the acquired resistance to doxorubicin in DU145 prostate carcinoma cells. Med Oncol 39, 194 (2022). https://doi.org/10.1007/s12032-022-01787-9

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