Anti-tumor effects of pEgr-1-endostatin-TNF-α recombinant plasmid expression induced by ionizing radiation

Asian Pac J Cancer Prev. 2011;12(11):2933-7.

Abstract

Purpose: The aim of the present study was to investigate the anti-tumor effect of a pEgr-1-endostatin-TNF-α recombinant plasmid induced by ionizing radiation.

Method: Three hundred and twenty mice bearing Lewis lung carcinomas were divided into four experimental groups: blank control, irradiation treatment, plasmid treatment and plasmid combined irradiation treatment. Twenty-four hours after the recombinant plasmid was injected locally into the tumors of the mice, they were irradiated with 10 Gy γ -rays. The concentration of TNF-α and endostatin in the serum of mice was measured by ELISA and tumor growth in each group was compared. The tumor microvessel density was examined by H and E staining and immunohistochemistry analysis of CD31 positive cells.

Results: Radiation could induce the expression of pEgr-1-endostatin-TNFα. The levels of endostatin and TNF-α could express steadily for about 4 weeks, with concentrations of 52.6 ± 4.19 and 12.0 ± 0.87 ng/ml respectively, in the second week in combined therapy group and maintained at relative higher level in the fourth week than other groups (F=29.7, P>0.05). Compared with the control group, the tumor micro vessel density was significantly depressed (P>0.05) and tumor growth was significantly inhibited (5907.2 ± 78.6 mm3 vs. 763.5 ± 12.3 mm3, P >0.05).

Conclusions: The expression of pEgr-1-endostatin-TNF-α could be induced in mice in vivo and exhibited more significant anti-tumor and anti-angiogenesis effects than irradiation alone.

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / genetics
  • Carcinoma, Lewis Lung / radiotherapy
  • Carcinoma, Lewis Lung / therapy*
  • Cell Proliferation
  • Early Growth Response Protein 1 / blood*
  • Early Growth Response Protein 1 / genetics
  • Endostatins / blood*
  • Endostatins / genetics
  • Gamma Rays*
  • Genetic Therapy / methods*
  • Mice
  • Neovascularization, Pathologic
  • Plasmids*
  • Platelet Endothelial Cell Adhesion Molecule-1 / blood
  • Tumor Necrosis Factor-alpha / blood*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Early Growth Response Protein 1
  • Egr1 protein, mouse
  • Endostatins
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Tumor Necrosis Factor-alpha