Anti-tumor effect of pEgr-IFNgamma gene-radiotherapy in B16 melanoma-bearing mice

World J Gastroenterol. 2004 Oct 15;10(20):3011-5. doi: 10.3748/wjg.v10.i20.3011.

Abstract

Aim: To construct a pEgr-IFNgamma plasmid and to investigate its expression properties of interferon-gamma (INF-gamma) induced by irradiation and the effect of gene-radiotherapy on the growth of melanoma.

Methods: A recombined plasmid, pEgr-IFNgamma, was constructed and transfected into B16 cell line with lipofectamine. The expression properties of pEgr-IFNgamma were investigated by ELISA. Then, a B16 melanoma-bearing model was established in mice, and the plasmid was injected into the tumor tissue. The tumor received 20 Gy X-ray irradiation 36 h after injection, and IFN-gamma expression was detected from the tumor tissue. A tumor growth curve at different time points was determined.

Results: The eukaryotic expression vector, pEgr-IFNgamma, was successfully constructed and transfected into B16 cells. IFN-gamma expression was significantly increased in transfected cells after X-ray irradiation in comparison with 0 Gy group (77.73-94.60 pg/mL, P<0.05-0.001), and was significantly higher at 4 h and 6 h than that of control group after 2 Gy X-ray irradiation (78.90-90.00 pg/mL, P<0.01-0.001). When the transfected cells were given 2 Gy irradiation 5 times at an interval of 24 h, IFN-gamma expression decreased in a time-dependent manner. From d 3 to d 15 after IFNgamma gene-radiotherapy, the tumor growth was significantly slower than that after irradiation or gene therapy alone.

Conclusion: The anti-tumor effect of pEgr-IFNgamma gene-radiotherapy is better than that of genetherapy or radiotherapy alone for melanoma. These results may establish an important experimental basis for gene-radiotherapy of cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • Combined Modality Therapy
  • DNA-Binding Proteins / genetics
  • Early Growth Response Protein 1
  • Genetic Therapy*
  • Immediate-Early Proteins / genetics
  • Interferon-gamma / therapeutic use*
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / radiotherapy
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred Strains
  • Plasmids
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / genetics

Substances

  • Antiviral Agents
  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Immediate-Early Proteins
  • RNA, Messenger
  • Transcription Factors
  • Interferon-gamma