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

Abstract

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.

• Authors: H Jiang, L Zhang, J Liu, Z Chen, R Na, G Ding, H Zhang, Q Ding
• Journal: Cancer gene therapy (Cancer Gene Ther) Vol. 19 Issue 10 Pg. 684-9 (Oct 2012) ISSN: 1476-5500 [Electronic] England
• PMID: 22898899 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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