ENHANCEMENT OF ANTICANCER EFFECTS OF RADIATION AND CONVENTIONAL ANTICANCER AGENTS BY A QUINOLINONE DERIVATIVE, VESNARINONE - STUDIES ON HUMAN GASTRIC-CANCER TISSUE XENOGRAFTS IN NUDE-MICE

methoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone), a quinolinone deriv ative, is an orally active inotropic agent used in Japan for the treat ment of chronic heart failure. Recently, it has been reported that ves narinone induces differentiation and apoptosis in certain types of leu kaemia and solid tumour cells, and exhibits antitumour effect on sever al tumours xenografted in nude mice. In the present study, we examined the antitumour effect of vesnarinone in combination with radiation an d conventional anticancer agents in nude mice xenografted with human g astric carcinoma, a poorly-differentiated adenocarcinoma, MKN-45 cell line which has a wild-type p53 gene. Vesnarinone treatment combined wi th radiation resulted in a higher antitumour activity compared with a single treatment with either vesnarinone or radiation alone. Further, vesnarinone treatment together with radiation and conventional antican cer agents including 5-FU and picibanil (an immunopotentiator) produce d the highest antitumour effect compared with any other treatment. Add itionally, the combination treatment induced marked differentiation an d apoptosis of the tumour cells and an increase in the expression of p 53 gene in the treated tumour cell's. The results suggest that vesnari none, in combination with radiation and the conventional antitumour ag ents, may be of clinical interest for treatment of certain types of ga stric tumours.