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. 2025 Jan-Feb;19(1):15579883241310834.
doi: 10.1177/15579883241310834.

Cyclosporine A Decreased Paclitaxel Resistance in Prostate Cancer Cells by Inhibiting MTDH Expression

Jiangtao Li  1 , Yuzhi Li  1 , Xiaohong Zhang  2 , Kun Liu  3 , Shiping Yang  1 , Zhang Liu  3 , Sheng Cao  3 , Dongfei Ren  4 , Menghui Cui  1 , Jia Su  3 , Zewang Zhen  3 , Donghong Zhang  5
Affiliations

Cyclosporine A Decreased Paclitaxel Resistance in Prostate Cancer Cells by Inhibiting MTDH Expression

Jiangtao Li et al. Am J Mens Health. 2025 Jan-Feb.

Abstract

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.

Keywords: MTDH; cyclosporine A; drug resistance; paclitaxel; prostate cancer.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
CsA Reduces Paclitaxel Resistance in Prostate Cancer Cells. (A, B) Establishment of Paclitaxel-Resistant Cell Lines PC-3-R (A) and LNCaP-3-R (B). (C, D) CsA Can Reduce Paclitaxel Resistance in PC-3-R (C) and LNCaP-3-R (D) ***p < .001.
Figure 2.
Figure 2.
CsA Can Reduce MTDH Protein Expression. (A) Western Blot Results for Expression of MTDH in Cells. (B) mRNA Expression of MTDH in Cells. (C, D) Treatment of PC-3-R (C) and LNCaP-3-R (D) Cells With a CsA Gradient for 48 hr Decreased MTDH Protein Expression. (E, F) Treatment of PC-3-R (E) and LNCaP-3-R (F) With a CsA Gradient for 48 hr Decreased the mRNA Expression Level of MTDH *p < .05. **p < .01. ***p < .001.
Figure 3.
Figure 3.
Overexpression of MTDH Increases Paclitaxel Resistance in Prostate Cancer Cells. (A, B) Validation of Western Blot Results for Overexpression of MTDH in PC-3-R (A) and LNCaP-3-R (B) Cells. (C, D) Overexpression of MTDH Increases the MTT Results of Paclitaxel Resistance in PC-3-R (C) and LNCaP-3-R (D) Cells. (E, F) Overexpression of MTDH Increases the Colony Formation Number of PC-3-R (E) and LNCaP-3-R (F) Cells ***p < .001.
Figure 4.
Figure 4.
Knockdown of MTDH Reduces Paclitaxel Resistance in Prostate Cancer Cells. (A, B) Validation of Western Blot Results for MTDH Knockdown in PC-3-R (A) and LNCaP-3-R (B) Cells. (C, D) Knockdown of MTDH Reduced the MTT Results of Paclitaxel Resistance in PC-3-R (C) and LNCaP-3-R (D) Cells. (E, F) Knockdown of MTDH Reduced the Colony Formation Number of PC-3-R (E) and LNCaP-3-R (F) Cells ***p < .001.
Figure 5.
Figure 5.
MTDH Reduces Paclitaxel Resistance in Prostate Cancer Cells In Vivo. (A) Nude Mouse Xenograft Experiments Were Performed Using PC-3-R Cells Treatment With Paclitaxel. n = 5 Mice. (B) Statistics of Tumor Volume in Xenograft Experiments in Nude Mice. (C) Statistics of Tumor Weight in Xenograft Experiments in Nude Mice. (D) Nude Mouse Xenograft Experiments Were Performed Using PC-3-R Cells Treatment With Paclitaxel. n = 5 Mice. (E) Statistics of Tumor Volume in Xenograft Experiments in Nude Mice. (F) Statistics of Tumor Weight in Xenograft Experiments in Nude Mice. (G) Expression of MTDH in Tumors Note. ns = not significant. ***p < .001.
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