ENHANCEMENT OF CHEMOSENSITIVITY TOWARD ANTICANCER DRUGS BY HIGH EXPRESSION OF CASPASE-1 IN NIH 3T3 CELLS

It has been well documented that caspase-1 (interleukin-1 beta-convert ing enzyme, ICE) and its related cysteine proteinases such as caspase- 3 (CPP32, apopain) and caspase-2 (ICH-1(L)) play important roles in ap optosis. In the present study, these genes were inserted into an induc ible eukaryotic expression vector, pMSG, and transfected into NIH 3T3 mouse fibroblasts. The expression of caspases-1 and -3 was effectively induced by treatment with dexamethasone (Dex). The expression of casp ase-2 was elevated in the transfected cells without treatment with Dex but was not further stimulated by Dex. High expression of these prote ases alone induced neither apoptosis-like cell death nor any morpholog ical change. However, the expression of caspase-1 but not of caspase-2 or -3 enhanced chemosensitivity toward cytotoxic anticancer drugs suc h as aclarubicin, epirubicin, adriamycin, nimustine and ifosfamide. It is thus concluded that caspase-1 mediates cytotoxic effects of these drugs. [(C) 1998 Rapid Science Ltd.].