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International Journal of Oncology
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Article

Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer

  • Authors:
    • Bo Yin
    • Mo Zhang
    • Yu Zeng
    • Youqiang Li
    • Chao Zhang
    • Yongsheng Song
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China, Department of Urology, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21087, USA
  • Pages: 1730-1736
    |
    Published online on: February 17, 2016
       https://doi.org/10.3892/ijo.2016.3396
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Abstract

Paclitaxel frequently serves as the first-line chemotherapeutic agent for castration-resistant prostate cancer (PCa) patients. However, acquired paclitaxel-resistance almost always occurs after initial responses, and the mechanisms by which this occurs remain largely unknown. The goal of the present study was to identify differentially expressed protein(s) associated with paclitaxel-resistance and further explore the potential mechanisms involved in drug resistance. By comparing the nuclear matrix protein (NMP) patterns of DU145-TxR cells, the previously established stable paclitaxel-resistant PCa cells, with that of the parental DU145 cells using two-dimensional electrophoresis, we found that cytokeratin 18 (CK18) is downregulated in DU145-TxR cells. The downregulation of CK18 in DU145-TxR cells at mRNA, NMP and total cellular protein levels was validated by real-time RT-PCR, immunoblotting and immunofluorescence, indicating that the downregulation of CK18 was a global effect in DU145-TxR cells due to paclitaxel-resistance. Furthermore, in vivo assay of xenograft transplantation confirmed the higher tumorigenicity of DU145-TxR cells, suggesting that these paclitaxel-resistant PCa cells possessed potent cancer stem cell (CSC)-like properties and eventually developed paclitaxel-resistance. Moreover, we determined by immunohistochemistry that CK18 expression in PCa tissues was inversely correlated with tumor grade in a statistically significant fashion, indicating a potential association of the downregulation of CK18 with tumor aggressiveness. Therefore, further study to define the potential role of CK18 may lead to novel therapy strategies as well as clinically useful biomarker for PCa patients.
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Copy and paste a formatted citation
Spandidos Publications style
Yin B, Zhang M, Zeng Y, Li Y, Zhang C and Song Y: Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer. Int J Oncol 48: 1730-1736, 2016.
APA
Yin, B., Zhang, M., Zeng, Y., Li, Y., Zhang, C., & Song, Y. (2016). Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer. International Journal of Oncology, 48, 1730-1736. https://doi.org/10.3892/ijo.2016.3396
MLA
Yin, B., Zhang, M., Zeng, Y., Li, Y., Zhang, C., Song, Y."Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer". International Journal of Oncology 48.4 (2016): 1730-1736.
Chicago
Yin, B., Zhang, M., Zeng, Y., Li, Y., Zhang, C., Song, Y."Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer". International Journal of Oncology 48, no. 4 (2016): 1730-1736. https://doi.org/10.3892/ijo.2016.3396
Copy and paste a formatted citation
x
Spandidos Publications style
Yin B, Zhang M, Zeng Y, Li Y, Zhang C and Song Y: Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer. Int J Oncol 48: 1730-1736, 2016.
APA
Yin, B., Zhang, M., Zeng, Y., Li, Y., Zhang, C., & Song, Y. (2016). Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer. International Journal of Oncology, 48, 1730-1736. https://doi.org/10.3892/ijo.2016.3396
MLA
Yin, B., Zhang, M., Zeng, Y., Li, Y., Zhang, C., Song, Y."Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer". International Journal of Oncology 48.4 (2016): 1730-1736.
Chicago
Yin, B., Zhang, M., Zeng, Y., Li, Y., Zhang, C., Song, Y."Downregulation of cytokeratin 18 is associated with paclitaxel‑resistance and tumor aggressiveness in prostate cancer". International Journal of Oncology 48, no. 4 (2016): 1730-1736. https://doi.org/10.3892/ijo.2016.3396
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