Cancer gene therapy using a pro-apoptotic gene, caspase-3

Caspase-3 is a member of the cysteine protease family, which plays a crucia l role in apoptosis. We applied the human caspase-3 gene as a novel form of anticancer gene therapy. Overexpression of human caspase-3 alone could not induce apoptosis of tumor cell lines, but apoptosis was markedly enhanced by the addition of etoposide. In an AH130 liver tumor model. transduction o f human caspase-3 but not the empty vector, induced extensive apoptosis and reduced tumor volume when combined with etoposide administration. However this effect was not observed with a Bcl-2 overexpressing tumor. In conclusi on, caspase-3 gene transduction accompanied by an additional death stimulus may be a useful method of anticancer gene therapy, except for Bcl-2 overex pressing tumors.