Advertisement

Radiation and Environmental Biophysics

, Volume 49, Issue 4, pp 705–714 | Cite as

Anti-tumor effect of 125I-UdR in combination with Egr-1 promoter-based IFNγ gene therapy in vivo

  • Wei Yang
  • Jing-Guo Zhao
  • Xiu-Yi Li
  • Shou-Liang Gong
  • Jian-Ping Cao
Original Paper

Abstract

Although 125I-UdR treatment of malignant tumors in animal models and patients has achieved a certain effect, the short half-life of 125I-UdR in vivo and its cellular uptake only in S phase of the cell cycle are limiting factors with regard to tumor eradication, and therefore its combination with other applications is a promising strategy in cancer therapy. In this study, we show that 125I-UdR radionuclide therapy in combination with Egr-1 promoter-based IFNγ gene therapy is more effective than 125I-UdR therapy alone in suppressing tumor growth and extending survival duration in mice bearing H22 hepatomas. Combined therapy could significantly inhibit cell proliferation and tumor angiogenesis, induce apoptosis and enhance cytotoxic activities of splenic CTL of the mice. Our results suggest that 125I-UdR in combination with Egr-1 promoter-based IFNγ gene therapy may provide novel approaches for cancer treatment.

Keywords

Proliferate Cell Nuclear Antigen KeyGen Biotech Tumor Inhibition Rate Gene Therapy Group 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors thank Dr. L. Sun (School of Radiological Medicine and Public Health, Soochow University) for valuable advice on this manuscript. This work was supported by the National Natural Science Foundation of China (No. 30600160) and Program for Changjiang Scholars and Innovative Research Team in University (IRT0849). The authors declare that they have no conflict of interest.

References

  1. Angiolillo A, Sgadari C, Tosato G (1996) A role for the interferon-inducible protein 10 in inhibition of angiogenesis by interleukin-12. Ann N Y Acad Sci 795:158–167CrossRefADSGoogle Scholar
  2. Baranowska-Kortylewicz J, Makrigiorgos GM, Van den Abbeele AD, Berman RM, Adelstein SJ, Kassis AI (1991) 5-[123I]iodo-2’-deoxyuridine in the radiotherapy of an early ascites tumor model. Int J Radiat Oncol Biol Phys 21:1541–1551Google Scholar
  3. Buchegger F, Adamer F, Schaffland AO, Kosinski M, Grannavel C, Dupertuis YM, de Tribolet N, Mach JP, Delaloye AB (2004) Highly efficient DNA incorporation of intratumourally injected [125I]iododeoxyuridine under thymidine synthesis blocking in human glioblastoma xenografts. Int J Cancer 110:145–149CrossRefGoogle Scholar
  4. Chien PY, Wang J, Carbonaro D, Lei S, Miller B, Sheikh S, Ali SM, Ahmad MU, Ahmad I (2005) Novel cationic cardiolipin analogue-based liposome for efficient DNA and small interfering RNA delivery in vitro and in vivo. Cancer Gene Ther 12:321–328CrossRefGoogle Scholar
  5. Datta R, Rubin E, Sukhatme V, Qureshi S, Hallahan D, Weichselbaum RR, Kufe DW (1992) Ionizing radiation activates transcription of the EGR1 gene via CArG elements. Proc Natl Acad Sci 89:10149–10153CrossRefADSGoogle Scholar
  6. Datta R, Taneja N, Sukhatme VP, Qureshi SA, Weichselbaum R, Kufe DW (1993) Reactive oxygen intermediates target CC(A/T)6GG sequences to mediate activation of the early growth response 1 transcription factor gene by ionizing radiation. Proc Natl Acad Sci 90:2419–2422CrossRefADSGoogle Scholar
  7. Hallahan DE, Mauceri HJ, Seung LP, Dunphy EJ, Wayne JD, Hanna NN, Toledano A, Hellman S, Kufe DW, Weichselbaum RR (1995) Spatial and temporal control of gene therapy using ionizing radiation. Nat Med 1:786–791CrossRefGoogle Scholar
  8. Horton MR, McKee CM, Bao C, Liao F, Farber JM, Hodge-DuFour J, Puré E, Oliver BL, Wright TM, Noble PW (1998) Hyaluronan fragments synergize with interferon-gamma to induce the C-X-C chemikines mig and interferon-inducible protein-10 in mouse macrophages. J Biol Chem 273:35088–35094CrossRefGoogle Scholar
  9. Kassis AI (2003) Cancer therapy with auger electrons: are we almost there? J Nucl Med 44:1479–1481Google Scholar
  10. Kassis AI, Sastry KSR, Adelstein SJ (1987a) Kinetics of uptake, retention, and radiotoxicity of 125IUdR in mammalian cells: implications of localized energy deposition by Auger processes. Radiat Res 10:78–89CrossRefGoogle Scholar
  11. Kassis AI, Fayad F, Kinsey BM, Sastry KSR, Taube RA, Adelstein SJ (1987b) Radiotoxicity of 125I in mammalian cells. Radiat Res 11:305–318CrossRefGoogle Scholar
  12. Kassis AI, Dahman BA, Adelstein SJ (2000) In vivo therapy of neoplastic meningitis with methotrexate and 5-[125I]iodo-2’-deoxyuridine. Acta Oncol 39:731–737CrossRefGoogle Scholar
  13. Kawashita Y, Ohtsuru A, Miki F, Kuroda H, Morishita M, Kaneda Y, Hatsushiba K, Kanematsu T, Yamashita S (2005) Eradication of hepatocellular carcinoma xenografts by radiolabelled, lipiodol-inducible gene therapy. Gene Ther 12:1633–1639CrossRefGoogle Scholar
  14. Keough WG, Hofer KG (1978) An improved method for synthesis and purification of 125I or 131I labeled carrier-free 5-iodo-2’-deoxyuridine. J Labelled Comp Radiopharm 14:83–90CrossRefGoogle Scholar
  15. Koppe MJ, Bleichrodt RP, Soede AC, Verhofstad AA, Goldenberg DM, Oyen WJ, Boerman OC (2004) Biodistribution and therapeutic efficacy of 125/131I-, 186Re-, 88/90Y-, or 177Lu-labeled monoclonal antibody MN-14 to carcinoembryonic antigen in mice with small peritoneal metastases of colorectal origin. J Nucl Med 45:1224–1232Google Scholar
  16. Makrigiorgos GM, Kassis AI, Baranowska-Kortylewicz J, McElvany KD, Welch MJ, Sastry KS, Adelstein SJ (1989) Radiotoxicity of 5-[123I]iodo-2’-deoxyuridine in V79 cells: a comparison with 5-[125I]iodo-2’-deoxyuridine. Radiat Res 11:532–544CrossRefGoogle Scholar
  17. Manome Y, Kunieda T, Wen PY, Koga T, Kufe DW, Ohno T (1998) Transgene expression in malignant glioma using a replication-defective adenoviral vector containing the Egr-1 promoter: activation by ionizing radiation or uptake of radioactive iododeoxyuridine. Hum Gene Ther 9:1409–1417CrossRefGoogle Scholar
  18. Meidan VM, Glezer J, Salomon S, Sidi Y, Barenholz Y, Cohen JS, Lilling G (2006) Specific lipoplex-mediated antisense against Bcl-2 in breast cancer cells: a comparison between different formulations. J Liposome Res 16:27–43CrossRefGoogle Scholar
  19. Morille M, Passirani C, Vonarbourg A, Clavreul A, Benoit JP (2008) Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials 29:3477–3496CrossRefGoogle Scholar
  20. Semnani ES, Wang K, Adelstein SJ, Kassis AI (2005) 5-[123I/125I]Iodo-2’-deoxyuridine in metastatic lung cancer: radiopharmaceutical formulation affects targeting. J Nucl Med 46:800–806Google Scholar
  21. Stabin MG (1996) MIRDOSE: personal computer software for internal dose assessment in nuclear medicine. J Nucl Med 37:538–546Google Scholar
  22. Sukhatme VP (1990) Early transcriptional events in cell growth: the Egr family. J Am Soc Nephrol 1:859–866Google Scholar
  23. Takahashi T, Namiki Y, Ohno T (1997) Induction of the suicide HSV-TK gene by activation of the Egr-1 promoter with radioisotopes. Hum Gene Ther 8:827–833CrossRefGoogle Scholar
  24. Urashima T, Wang K, Adelstein SJ, Kassis AI (2004) Activation of diverse pathways to apoptosis by (125)IdUrd and gamma-photon exposure. Int J Radiat Biol 80:867–874CrossRefGoogle Scholar
  25. Weichselbaum RR, Hallahan DE, Beckett MA, Mauceri HJ, Lee H, Sukhatme VP, Kufe DW (1994) Gene therapy targeted by radiation preferentially radiosensitizes tumor cells. Cancer Res 54:4266–4269Google Scholar
  26. Weichselbaum RR, Kufe DW, Hellman S, Rasmussen HS, King CR, Fischer PH, Mauceri HJ (2002) Radiation-induced tumour necrosis factor-alpha expression: clinical application of transcriptional and physical targeting of gene therapy. Lancet Oncol 3:665–671CrossRefGoogle Scholar
  27. Wu JX, Xiao X, Zhao P, Xue G, Zhu YH, Zhu XF, Zheng LM, Zeng YX, Huang WL (2006) Minicircle-IFNgamma induces antiproliferative and antitumoral effects in human nasopharyngeal carcinoma. Clin Cancer Res 12:4702–4713CrossRefGoogle Scholar
  28. Wu DS, Wu CM, Huang TH, Xie QD (2008) Combined effects of radiotherapy and endostatin gene therapy in melanoma tumor model. Radiat Environ Biophys 47:285–291CrossRefGoogle Scholar
  29. Yang W, Li XY (2005) Anti-tumor effect of pEgr-IFNγ-Endostatin gene-radiotherapy in mice bearing Lewis lung carcinoma and its mechanism. Chin Med J 118:296–301Google Scholar
  30. Zhao JG, Yang W, Sun T, Zhang J, Li Y, Gao FT (2007a) Experimental study on radiation inducible expression of recombinant plasmid pcDNAEgr- IFNγ by ionizing radiation of 125I-UdR in vitro. Chin J Geront 27:501–503ADSGoogle Scholar
  31. Zhao P, Zhu YH, Wu JX, Liu RY, Zhu XY, Xiao X, Li HL, Huang BJ, Xie FJ, Chen JM, Ke ML, Huang W (2007b) Adenovirus-mediated delivery of human IFNγ gene inhibits prostate cancer growth. Life Sci 81:695–701CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Wei Yang
    • 1
  • Jing-Guo Zhao
    • 2
  • Xiu-Yi Li
    • 3
  • Shou-Liang Gong
    • 3
  • Jian-Ping Cao
    • 1
  1. 1.Department of Radiobiology, School of Radiological Medicine and Public HealthSoochow UniversitySuzhouChina
  2. 2.Department of OrthopedicsPLA 403th HospitalDalianChina
  3. 3.MH Radiobiology Research Unit, School of Public HealthJilin UniversityChangchunChina

Personalised recommendations