Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran.
Med Oncol. 2022 Sep 7;39(12):194. doi: 10.1007/s12032-022-01787-9.
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 IC 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) 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.
本研究旨在评估环丙沙星（CIP）对多柔比星（DOX）耐药的去势抵抗性前列腺癌 DU145 细胞的影响。通过将 DU145 细胞暴露于递增浓度的 DOX 来建立 DOX 耐药的 DU145（DU145/DOX20）细胞。通过 MTT、集落形成和 3D 培养测定来检查 CIP 的抗增殖作用。与 DU145 细胞相比，DU145/DOX20 细胞对 DOX 的 IC 值增加了两倍，ABCB1 转运体活性增加，并且形态发生了一些变化，伴随球体大小、黏附和迁移潜力降低。与 DU145 细胞相比，CIP（5 和 25μg/mL）导致 DU145/DOX20 细胞活力的降低更为显著。与 2D 培养相比，DU145/DOX20 细胞在 3D 培养中对 CIP 的耐药性更高。用 DOX 和 CIP 组合处理的 DU145/DOX20 细胞未形成球体。CIP 单独或与 DOX 联合使用可显著减少 DU145 球体的生长。CIP 与 20 nM DOX 联合使用可防止 DU145 细胞的集落形成。由于 DU145/DOX20 细胞的黏附潜力低，无法估计其克隆形成能力。CIP 单独使用可显著降低 DU145 细胞的迁移，并导致暴露于 DOX 的细胞的伤口闭合能力更严重下降。我们确定 CIP 增强了 DU145 和 DU145/DOX20 细胞对 DOX 的敏感性。本研究表明，低浓度 CIP 和 DOX 的联合递送可能是治疗 DOX 耐药和敏感的去势抵抗性前列腺癌的一种有前途的策略。
