TNP-470 INHIBITS COLLATERALIZATION TO COMPLEMENT THE ANTITUMOR EFFECTOF HEPATIC-ARTERY LIGATION

We examined hepatic artery ligation combined with an angiogenesis inhi bitor, TNP-470, in the treatment of VX2 tumour inoculated into the liv er of rabbits. Effects on tumour growth were correlated with arterial collateral development in this system. Three treatment methods were co mpared: (1) the left hepatic artery was ligated at the liver hilum (li gation group); (2) TNP-470 (40 mg per body) was infused continuously f or 7 days via the common hepatic artery (TNP group); (3) the left hepa tic artery was ligated and TNP-470 was infused continuously for 7 days via the common hepatic artery (ligation + TNP group). These treatment s were started 12-14 days after tumour inoculation. The day of initiat ing treatment was defined as day 0, Although there were no significant differences in tumour volume among the three treated groups on day 7 after treatment, tumour Volumes in the ligation + INP group were signi ficantly smaller than in the ligation group and the TNP group on day 1 4 after treatment. The vasculature and arterial collaterals around the tumour were demonstrated by the perfusion of a silicon rubber solutio n, Microfil. In the ligation + TNP group, the new microvasculature aro und the tumour decreased compared with the ligation group. The TNP-470 inhibition of microvascular proliferation may limit the development o f collaterals that communicate with new feeding arteries. These result s suggest that transarterial embolization combined with TNP-470 may en hance the anti-tumour effect of transarterial embolization alone in th e treatment of liver tumours.