Induction of interleukin 2 expression in the liver for the treatment of H22 hepatoma in mice

Abstract

Background and aims: We designed this study to evaluate the ability of a plasmid carrying an RU486 regulatory system to induce expression of interleukin-2 (IL-2) gene and to examine the antitumour efficacy of the induced IL-2 gene.

Methods: The plasmid pRS-mIL-2,which contains an RU486 inducible system and IL-2 gene was injected into mice. Sera and tissues from liver, spleen, lungs and kidneys were taken to test the properties of the plasmid. To examine the antitumour efficacy of pRS-mIL-2, tumours were established in the liver by direct inoculation of H22 hepatoma cells.

Results: The IL-2 levels in serum correlated with the dose of plasmid and RU486. High and sustained IL-2 levels could be achieved by administration of RU486 every day. The mRNA of transgene IL-2 was found only in the liver. Treatment of mice with pRS-mIL-2 plus RU486 resulted in the significant reduction in tumour volume compared with control groups.

Conclusions: Tight temporal and spatial control of transgene IL-2 expression can be achieved by a plasmid containing an RU486 inducible system driven by liver specific promoter. pRS-mIL-2 exhibited strong antitumour efficacy following consecutive induction with RU486.