Li Jiangtao, Li Yuzhi, Zhang Xiaohong, Liu Kun, Yang Shiping, Liu Zhang, Cao Sheng, Ren Dongfei, Cui Menghui, Su Jia, Zhen Zewang, Zhang Donghong
Department of Urinary Surgery, Hebei Eighth People's Hospital, Shijiazhuang, China.
Department of General Physician, Hebei Eighth People's Hospital, Shijiazhuang, China.
Am J Mens Health. 2025 Jan-Feb;19(1):15579883241310834. doi: 10.1177/15579883241310834.
This study aims to investigate the effect and mechanism of cyclosporine A (CsA) on paclitaxel-resistant prostate cancer cells. Paclitaxel-resistant prostate cancer cell lines were established by gradual increment method. The proliferation of cells was tested using MTT and colony formation assay. Western blot was used to detect protein expression. Expression levels of gene mRNA were detected using real-time polymerase chain reaction (RT-PCR). Xenografts in nude mice were used to validate the conclusion in vitro. The results showed that CsA could increase the sensitivity of prostate cancer cells to paclitaxel. Treatment of paclitaxel-resistant prostate cancer cell lines with CsA gradients decreased metadherin (MTDH) protein expression. RT-PCR showed that CsA could decrease the mRNA level of MTDH. Overexpression of MTDH in prostate cancer cells increases paclitaxel resistance in prostate cancer cells. Conversely, knockdown of MTDH reduced paclitaxel resistance in prostate cancer cells. Treating cells with CsA failed to reduce paclitaxel resistance in prostate cancer cells when MTDH was overexpressed. Xenografts in nude mice yielded consistent conclusions with the in vitro results. In conclusion, CsA can reduce the resistance of prostate cancer cells to paclitaxel. In vitro and in vivo experiments have shown that CsA can reduce paclitaxel resistance in prostate cancer cells by decreasing MTDH expression. In clinical practice, CsA can be used in combination with paclitaxel to improve the therapeutic effect on prostate cancer. MTDH may serve as a novel target for treating paclitaxel resistance in prostate cancer.
本研究旨在探讨环孢素A（CsA）对紫杉醇耐药前列腺癌细胞的作用及机制。采用逐步递增法建立紫杉醇耐药前列腺癌细胞系。使用MTT法和集落形成试验检测细胞增殖。采用蛋白质免疫印迹法检测蛋白表达。使用实时聚合酶链反应（RT-PCR）检测基因mRNA表达水平。利用裸鼠异种移植模型验证体外实验结论。结果表明，CsA可提高前列腺癌细胞对紫杉醇的敏感性。用不同浓度CsA处理紫杉醇耐药前列腺癌细胞系可降低黏附分子（MTDH）蛋白表达。RT-PCR结果显示，CsA可降低MTDH的mRNA水平。在前列腺癌细胞中过表达MTDH可增加前列腺癌细胞对紫杉醇的耐药性。相反，敲低MTDH可降低前列腺癌细胞对紫杉醇的耐药性。当MTDH过表达时，用CsA处理细胞不能降低前列腺癌细胞对紫杉醇的耐药性。裸鼠异种移植模型实验结果与体外实验结果一致。综上所述，CsA可降低前列腺癌细胞对紫杉醇的耐药性。体内外实验表明，CsA可通过降低MTDH表达来降低前列腺癌细胞对紫杉醇的耐药性。在临床实践中，CsA可与紫杉醇联合使用，以提高对前列腺癌的治疗效果。MTDH可能成为治疗前列腺癌紫杉醇耐药的新靶点。
