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Establishment of CXCR4-small interfering RNA retrovirus vector driven by human prostate-specific antigen promoter and its biological effects on prostate cancer in vitro and in vivo

Journal of Cancer Research and Clinical Oncology volume 134, pages 1255–1264 (2008)Cite this article

An Erratum to this article was published on 01 October 2008

Abstract

Purpose

CXC chemokine receptor-4 (CXCR4) is closely involved in bone metastasis of prostate cancer, and CXCR4 levels are frequently increased in prostate cancer cells and tissues. In the present study, its biological effects on prostate cancer in vitro and in vivo and feasibility to be a therapy target were investigated using a RNA interfering retrovirus vector targeting CXCR4 gene driven by human prostate-specific antigen promoter (pPSA).

Methods

We established a pPSA-siCXCR4 retrovirus vector and transfected prostate cancer cell PC-3m, LNCaP and breast cancer cell MCF-7, respectively. The expression of CXCR4 mRNA and protein was detected by RT-PCR and western blot, and the ability of adhesion, migration, invasion of prostate cancer cells was assessed using Transwell chamber. A metastasizing model using BALB/cA mice with human bone tissue implantation was established too, and transfected prostate cancer cells were via caudal vein. Survival time of mice suffering bone metastatic tumor as well as the weight and volume of these tumors were recorded and analyzed.

Results

The expression of CXCR4 mRNA and protein in androgen-responsive LNCaP cells was blocked by the pPSA-siCXCR4 vector, but it could not work in non androgen-responsive PC-3m cell and breast cancer cell MCF-7. The results of experiments in vitro also showed that the adhesion, transendothelial migration and invasive ability of transfected LNCaP cells were impaired, while there was no change in PC-3m and MCF-7 cells after transfection. pPSA-siCXCR4 represented a similar inhibitory effect in fluorescent bone metastasis model of LNCaP cells compared with PC-3m cells.

Conclusion

These results suggest that the downstream siRNA controlled by PSA promoter in retrovirus system can express selectively in androgen-responsive prostate cancer in vitro and in vivo, and CXCR4 plays an important role in prostate cancer metastasis. We believe that the pPSA-siCXCR4 retrovirus vector is a potential choice in gene therapy for androgen-responsive prostate cancer.

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Affiliations

  1. Department of Urology, The First Hospital Affiliated to Xi’an Jiaotong University, Yanta West Road 277#, Xi’an, Shanxi, 710061, China

    Yue-feng Du

  2. Department of Urology, Union Hospital, Tongji Medical College, Huanzhong University of Science and Technology, Wuhan, 430022, China

    Ying Shi, Yi-fei Xing & Fu-qing Zeng

Authors
  1. Yue-feng Du
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  2. Ying Shi
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  3. Yi-fei Xing
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  4. Fu-qing Zeng
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Correspondence to Yue-feng Du.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1007/s00432-008-0489-9

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Du, Yf., Shi, Y., Xing, Yf. et al. Establishment of CXCR4-small interfering RNA retrovirus vector driven by human prostate-specific antigen promoter and its biological effects on prostate cancer in vitro and in vivo. J Cancer Res Clin Oncol 134, 1255–1264 (2008). https://doi.org/10.1007/s00432-008-0394-2

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  • DOI: https://doi.org/10.1007/s00432-008-0394-2

Keywords

  • RNA interference
  • CXCR4
  • PSA
  • Prostate cancer
  • Metastasis