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STAT3 Decoy ODN Therapy for Cancer

Part of the Methods in Molecular Biology book series (MIMB, volume 1317)

Abstract

As an oncogene, over-activated signal transducer and activator of transcription 3 (STAT3) has been detected in many tumors. STAT3 controls cell differentiation, proliferation, and survival, and is associated with angiogenesis and immune dysfunction during tumorigenesis. Double-stranded decoy oligodeoxynucleotide (ODN) targeting over-activated STAT3 in tumor cells have shown significant antitumor efficiency. Here, we describe the materials and methods involved in STAT3 decoy ODN therapy for cancer including both the antitumor effect directly and immunotherapy indirectly.

Key words

STAT3 Decoy ODN Gene therapy Cancer 

Notes

Acknowledgement

This work was supported by Natural Science Foundation of China (#30628014; #30571696, #81172789, #30972692) and National 973 Science Program by Ministry of Science and Technology of China (2004CB518807).

References

  1. 1.
    Bowman T, Garcia R, Turkson J et al (2000) STATs in oncogenesis. Oncogene 19:2474–2488PubMedCrossRefGoogle Scholar
  2. 2.
    Yu H, Jove R (2004) The STATs of cancer—new molecular targets come of age. Nat Rev Cancer 4:97–105PubMedCrossRefGoogle Scholar
  3. 3.
    Bromberg J Jr, Darnell JE (2000) The role of STATs in transcriptional control and their impact on cellular function. Oncogene 19:2648–2673CrossRefGoogle Scholar
  4. 4.
    Zhang X, Zhang J, Wang L et al (2007) Therapeutic effects of STAT3 decoy oligodeoxynucleotide on human lung cancer in xenograft mice. BMC Cancer 7:149PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Su Y, Li G, Zhang X et al (2008) JSI-124 inhibits glioblastoma multiforme cell proliferation through G(2)/M cell cycle arrest and apoptosis augment. Cancer Biol Ther 7:1243–1249PubMedCrossRefGoogle Scholar
  6. 6.
    Sun X, Zhang J, Wang L et al (2008) Growth inhibition of human hepatocellular carcinoma cells by blocking STAT3 activation with decoy-ODN. Cancer Lett 262:201–213PubMedCrossRefGoogle Scholar
  7. 7.
    Kong LY, Gelbard A, Wei J et al (2010) Inhibition of p-STAT3 enhances IFN-alpha efficacy against metastatic melanoma in a murine model. Clin Cancer Res 16:2550–2561PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Tkach M, Coria L, Rosemblit C et al (2012) Targeting Stat3 induces senescence in tumor cells and elicits prophylactic and therapeutic immune responses against breast cancer growth mediated by NK cells and CD4+ T cells. J Immunol 189:1162–1172PubMedCrossRefGoogle Scholar
  9. 9.
    Bedel R, Thiery-Vuillemin A, Grandclement C et al (2011) Novel role for STAT3 in transcriptional regulation of NK immune cell targeting receptor MICA on cancer cells. Cancer Res 71:1615–1626PubMedCrossRefGoogle Scholar
  10. 10.
    Sun X, Sui Q, Zhang C et al (2013) Targeting blockage of STAT3 in HCC cells augments NK cell functions via reverse HCC-induced immune suppression. Mol Cancer Ther 12:2885–2896PubMedCrossRefGoogle Scholar
  11. 11.
    Shimizu H, Nakagami H, Tsukamoto I et al (2006) NFkappaB decoy oligodeoxynucleotides ameliorates osteoporosis through inhibition of activation and differentiation of osteoclasts. Gene Ther 13:933–941PubMedCrossRefGoogle Scholar
  12. 12.
    Leong PL, Andrews GA, Johnson DE et al (2003) Targeted inhibition of Stat3 with a decoy oligonucleotide abrogates head and neck cancer cell grow. Proc Natl Acad Sci U S A 100:4138–4143PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 25:402–408PubMedCrossRefGoogle Scholar
  14. 14.
    Jiang W, Sun R, Wei H, Tian Z et al (2005) Toll-like receptor 3 ligand attenuates LPS-induced liver injury by down-regulation of toll like receptor 4 expression on macrophages. Proc Natl Acad Sci U S A 102:17077–17082PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Biology Department, Shandong Quality Inspection Center For Medical DevicesJinanChina
  2. 2.Institute of Immunopharmacology & Immunotherapy, School of Pharmaceutical Sciences, Shandong UniversityJinanChina

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