Effects of quinolinone derivative, vesnarinone, in combination with irradiation on human lung cancer cell lines

The quinolinone derivative, vesnarinone, is a novel inotropic agent used in the treatment of heart failure. It has also been found that vesnarinone ha s a potential anti-cancer activity. To evaluate the anti-cancer activity of vesnarinone in combination with irradiation, we investigated the cytostati c and cytotoxic effects on human lung cancer cell lines (PC-9 and Lu 134A) using MTT assay and isobologram analysis. We also analyzed the nuclear frag mentation of tumor cells by flow cytometric analysis. Our study demonstrate d that combination of vesnarinone with irradiation had an additive inhibito ry effect on both PC-9 and Lu 134A tumor cell growth. Vesnarinone could imp rove the sensitivity of tumor cells to irradiation and thus the dose of irr adiation could be reduced to half without decreased inhibitory effect. Sign ificant increase of the tumor cell nuclear fragmentation was observed with combination of vesnarinone and irradiation. These results indicate that ves narinone not only directly inhibited tumor cell growth, but also improved t he sensitivity to irradiation. Combination of vesnarinone with irradiation may be an efficacious protocol for lung cancer treatment. The inhibitory ef fect was ascribed to inducing tumor cell apoptosis.