ENHANCEMENT OF THE ANTIPROLIFERATIVE ACTIVITY OF CIS-DIAMMINEDICHLOROPLATINUM(II) BY QUERCETIN

We have shown previously that the flavonoid quercetin (3,3′,4′,5,7‐pentahydroxyflavone) enhances the antiproliferative activity of cis‐diamminedichloroplatinum(II) (cis‐DDP) in vitro. In order to investigate whether this observation could be exploited in cancer treatment, we tested this drug combination in human tumor xenografts. The established human large‐cell cancer of the lung (LXFL 529) was implanted s.c. into nude mice. Tumors were allowed to grow to a mean diameter of approximately 5 mm and the animals were subsequently treated intraperitoneally with quercetin, cis‐DDP or a combination of both. Treatment was given 3 times at 3‐day intervals. Twenty milligrams quercetin per kg body weight caused no inhibition in tumor growth compared to untreated controls; 3 mg cis‐DDP per kg body weight with the same time schedule reduced tumor growth, compared to quercetin‐treated and control animals. Concomitant treatment with 20 mg quercetin and 3 mg cis‐DDP per kg body weight reduced tumor growth to a significantly greater degree than cis‐DDP alone. Toxicity of this treatment was relatively low as determined by measurements of the body weight of the mice. A combination of 4 mg or 5 mg cis‐DDP with 20 mg quercetin per kg body weight also reduced tumor growth compared to single cis‐DDP treatment. The toxicity of treatment with these increased doses was high, as shown by the high lethality and the loss of body weight of surviving animals. Copyright © 1990 Wiley‐Liss, Inc., A Wiley Company