Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9

Cancer Gene Ther. 2012 Oct;19(10):684-9. doi: 10.1038/cgt.2012.53. Epub 2012 Aug 17.


Zinc finger protein X-linked (ZFX) is a highly conservative mammalian gene with related functions in cell survival and proliferation. However, there are limited reports on regulation of ZFX as a therapeutic target in cancer treatment. In this study, the expression of ZFX in prostate cancer with matched normal adjacent tissues (n=45) and benign prostatic hyperplasia (BPH) tissues (n=16) were observed by immunohistochemical analysis. The effect of lentiviral siRNA (small interference RNA)-mediated dysfunction of ZFX on the proliferation of prostate cancer cells was studied. ZFX mRNA and protein expression levels in prostate cancer cells (PC-3 and DU145) were analyzed by western blotting and real-time polymerase chain reaction (RT-PCR). The effects of siRNA targeting ZFX on growth, cell cycle and apoptosis of PC-3 cells were evaluated by MTT assay and flow cytometry. We also investigated the effect of ZFX deletion on the activation of caspase-1, -3 and -9 by western blotting and colorimetric assay. Prostate cancer specimens appeared significantly higher (42.2% of cases being positive) than that observed in normal adjacent tissues (11.8% of cases being positive) and BPH tissues (12.5% of cases being positive). Repression of ZFX in the prostate cancer cells effectively suppressed the cellular proliferation and colony-formation ability, and led to G1 phase cell cycle arrest. Moreover, inhibition of ZFX-induced cell apoptosis by activating caspase-1, -3 and -9. In conclusion, ZFX represents the prominent role in the progression of prostate cancer and may be a promising therapy target for prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Caspase 3 / genetics
  • Caspase 3 / metabolism*
  • Caspase 9 / genetics
  • Caspase 9 / metabolism*
  • Cell Growth Processes / physiology
  • Enzyme Activation
  • Gene Knockdown Techniques
  • Humans
  • Immunohistochemistry
  • Kruppel-Like Transcription Factors / biosynthesis
  • Kruppel-Like Transcription Factors / deficiency*
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / metabolism
  • Male
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy*
  • Zinc Fingers


  • Kruppel-Like Transcription Factors
  • zinc finger protein, X-linked
  • Caspase 3
  • Caspase 9