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Molecular Medicine Reports
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August 2012 Volume 6 Issue 2

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Article

Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the treatment of breast cancer

  • Authors:
    • Guo-Qiang Su
    • Gang Su
    • Zong-Hai Huang
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The First Affiliated Hospital, Xiamen University, Xiamen 361003, P.R. China, Department of Cardiac Surgery, The First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, P.R. China, Department of General Surgery, The Affiliated Zhujiang Hospital, Nanfang Medical University, Guangzhou 510282, P.R. China
  • Pages: 321-329
    |
    Published online on: May 23, 2012
       https://doi.org/10.3892/mmr.2012.925
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Abstract

The aim of this study was to evaluate the selective killing efficacy of adenovirus (Ad)-mediated double suicide genes driven by the kinase domain-containing receptor (KDR) promoter in human breast cancer cells and vascular endothelial cells. Two Ad-mediated double suicide gene systems [with the two suicide genes, thymidine kinase (TK) and cytosine deaminase (CD)] with the KDR promoter (Ad-KDRP-CDglyTK) and the cytomegalovirus (CMV) promoter (Ad-CMV-CDglyTK) were established and transfected into the KDR-expressing MCF7 human breast cancer, EC304 human vascular endothelial and LS174T human colon carcinoma, which does not express KDR, cell lines. The selective killing efficiency and specificity of the double suicide gene system were measured in vitro by the analysis of cellular proliferation and assayed in vivo by subcutaneous injection of MCF7 cells into nude mice. The microvessel density (MVD) in the transplanted tumor was determined by immunohistochemical staining of CD34 cells. Our results showed that the transgenic CDglyTK genes were expressed in three cell lines (MCF7, ECV304 and LS174T) infected with Ad-CMV-CDglyTK. However, of the cells infected with Ad-KDRP-CDglyTK, the transgenic CDglyTK gene was only expressed in the KDR-expressing MCF7 and ECV304 cells, but not in the KDR-deficient LS174T cells. Cell proliferation was significantly reduced in a dose-dependent manner by pre-treatment with ganciclovir (GCV) and 5-fluorocytosine (5-FC) in MCF7 and ECV304 cells with transfected KDRP-CDglyTK genes and the three cell lines transfected with the CMV-CDglyTK genes. Similar results were not observed in the LS174T cells with transfected KDRP-CDglyTK genes. The results of this study show that the tumor-targeted expression of CDglyTK driven by the KDR promoter has a high specificity and performance. The killing effect of the CD/TK fusion gene in the target cells was significantly increased compared with the single suicide gene. The cell cycle of MCF7 and ECV304 cells transfected with KDRP-CDglyTK genes was arrested at the S phase following treatment with the prodrugs. The tumors formed by the MCF7 cells with the double suicide gene system were much smaller and the MVD of the tumor tissue was significantly decreased compared with the control. This study demonstrates that tumor‑targeted expression of the CDglyTK gene driven by the KDR promotor may be a novel strategy for the gene therapy of human breast cancer.
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1 

Sankaranarayanan R, Swaminathan R, Jayant K and Brenner H: An overview of cancer survival in Africa, Asia, the Caribbean and Central America: the case for investment in cancer health services. IARC Sci Publ. 162:257–291. 2011.PubMed/NCBI

2 

Gebbia V, Boussen H and Valerio MR: Oral metronomic cyclophosphamide with and without methotrexate as palliative treatment for patients with metastatic breast carcinoma. Anticancer Res. 32:529–536. 2012.PubMed/NCBI

3 

Mustacchi G, Cazzaniga ME, Pronzato P, et al: Breast cancer in elderly women: a different reality? Results from the NORA study. Ann Oncol. 18:991–996. 2007. View Article : Google Scholar : PubMed/NCBI

4 

Cocconi G, Caminiti C, Zaninetta G, et al: National survey of medical choices in caring for terminally ill patients in Italy, a cross-sectional study. Tumori. 96:122–130. 2010.PubMed/NCBI

5 

Chatterjee SJ and Pandey S: Chemo-resistant melanoma sensitized by tamoxifen to low dose curcumin treatment through induction of apoptosis and autophagy. Cancer Biol Ther. 11:216–228. 2011. View Article : Google Scholar : PubMed/NCBI

6 

Kim KY, Kim SU, Leung PC, et al: Influence of the prodrugs 5-fluorocytosine and CPT-11 on ovarian cancer cells using genetically engineered stem cells: tumor-tropic potential and inhibition of ovarian cancer cell growth. Cancer Sci. 101:955–962. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Tai CK, Wang W, Lai YH, et al: Enhanced efficiency of prodrug activation therapy by tumor-selective replicating retrovirus vectors armed with the Escherichia coli purine nucleoside phosphorylase gene. Cancer Gene Ther. 17:614–623. 2010. View Article : Google Scholar : PubMed/NCBI

8 

Kucerova L, Matuskova M, Hlubinova K, et al: Bystander cytotoxicity in human medullary thyroid carcinoma cells mediated by fusion yeast cytosine deaminase and 5-fluorocytosine. Cancer Lett. 311:101–112. 2011. View Article : Google Scholar

9 

Cottin S, Gould PV, Cantin L, et al: Gap junctions in human glioblastomas: implications for suicide gene therapy. Cancer Gene Ther. 18:674–681. 2011. View Article : Google Scholar : PubMed/NCBI

10 

Vernimmen D, Gueders M, Pisvin S, et al: Different mechanisms are implicated in ERBB2 gene overexpression in breast and in other cancers. Br J Cancer. 89:899–906. 2003. View Article : Google Scholar : PubMed/NCBI

11 

Tomizawa M, Yu L, Wada A, et al: A promoter region of the midkine gene that is frequently expressed in human hepatocellular carcinoma can activate a suicide gene as effectively as the alpha-fetoprotein promoter. Br J Cancer. 89:1086–1090. 2003. View Article : Google Scholar

12 

Beierle EA, Dai W, Langham MR Jr, et al: Expression of VEGF receptors in cocultured neuroblastoma cells. J Surg Res. 119:56–65. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Siemann DW and Shi W: Efficacy of combined antiangiogenic and vascular disrupting agents in treatment of solid tumors. Int J Radiat Oncol Biol Phys. 60:1233–1240. 2004. View Article : Google Scholar : PubMed/NCBI

14 

Ma J, Li M, Mei L, et al: Double suicide genes driven by kinase domain insert containing receptor promoter selectively kill human lung cancer cells. Genet Vaccines Ther. 9:1–6. 2011.PubMed/NCBI

15 

Yu Z, Wang H, Zhang L, et al: Both p53-PUMA/NOXA-Bax-mitochondrion and p53-p21cip1 pathways are involved in the CDglyTK-mediated tumor cell suppression. Biochem Biophys Res Commun. 386:607–611. 2009. View Article : Google Scholar : PubMed/NCBI

16 

Yang D, Yang J, Lu F, et al: A new membrane re-anchored protein originating from GPC3 against hepatoma cells HepG2. Mol Med Report. 4:1067–1073. 2011.PubMed/NCBI

17 

Huber BE, Austin EA, Good SS, et al: In vivo antitumor activity of 5-fluorocytosine on human colorectal carcinoma cells genetically modified to express cytosine deaminase. Cancer Res. 53:4619–4626. 1993.

18 

Weidner N, Folkman J, Pozza F, et al: Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. J Natl Cancer Inst. 84:1875–1887. 1992. View Article : Google Scholar : PubMed/NCBI

19 

Mauro LV, Bellido M, Morandi A, et al: Association between mast cells of different phenotypes and angiogenesis in colorectal cancer. Mol Med Report. 1:895–902. 2008.PubMed/NCBI

20 

Oh JY, Park MY, Kim DR, et al: Combination gene therapy of lung cancer with conditionally replicating adenovirus and adenovirus-herpes simplex virus thymidine kinase. Int J Mol Med. 25:369–376. 2010.PubMed/NCBI

21 

Ge YL, Zhang JY, Zhang X, et al: Chemically modified siRNA directed against the KDR gene inhibits the proliferation of breast cancer cells. Mol Med Report. 2:121–127. 2009.PubMed/NCBI

22 

Szary J, Kalita K, Przybyszewska M, et al: KDR promoter can transcriptionally target cytosine deaminase suicide gene to cancer cells of nonendothelial origin. Anticancer Res. 21:3471–3475. 2001.PubMed/NCBI

23 

Rogulski KR, Wing MS, Paielli DL, et al: Double suicide gene therapy augments the antitumor activity of a replication-competent lytic adenovirus through enhanced cytotoxicity and radiosensitization. Hum Gene Ther. 11:67–76. 2000. View Article : Google Scholar

24 

Qiu Y, Peng GL, Liu QC, et al: Selective killing of lung cancer cells using carcinoembryonic antigen promoter and double suicide genes, thymidine kinase and cytosine deaminase (pCEA-TK/CD). Cancer Lett. 316:31–38. 2012. View Article : Google Scholar

25 

Fischer U, Steffens S, Frank S, et al: Mechanisms of thymidine kinase/ganciclovir and cytosine deaminase/5-fluorocytosine suicide gene therapy-induced cell death in glioma cells. Oncogene. 24:1231–1243. 2005. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Su G, Su G and Huang Z: Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the treatment of breast cancer. Mol Med Rep 6: 321-329, 2012.
APA
Su, G., Su, G., & Huang, Z. (2012). Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the treatment of breast cancer. Molecular Medicine Reports, 6, 321-329. https://doi.org/10.3892/mmr.2012.925
MLA
Su, G., Su, G., Huang, Z."Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the treatment of breast cancer". Molecular Medicine Reports 6.2 (2012): 321-329.
Chicago
Su, G., Su, G., Huang, Z."Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the treatment of breast cancer". Molecular Medicine Reports 6, no. 2 (2012): 321-329. https://doi.org/10.3892/mmr.2012.925
Copy and paste a formatted citation
x
Spandidos Publications style
Su G, Su G and Huang Z: Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the treatment of breast cancer. Mol Med Rep 6: 321-329, 2012.
APA
Su, G., Su, G., & Huang, Z. (2012). Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the treatment of breast cancer. Molecular Medicine Reports, 6, 321-329. https://doi.org/10.3892/mmr.2012.925
MLA
Su, G., Su, G., Huang, Z."Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the treatment of breast cancer". Molecular Medicine Reports 6.2 (2012): 321-329.
Chicago
Su, G., Su, G., Huang, Z."Adenovirus-mediated tissue-targeted expression of the CDglyTk gene for the treatment of breast cancer". Molecular Medicine Reports 6, no. 2 (2012): 321-329. https://doi.org/10.3892/mmr.2012.925
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