SUPPRESSION OF HUMAN PANCREATIC-CANCER GROWTH IN BALB C NUDE-MICE BY MANUMYCIN, A FARNESYL-PROTEIN TRANSFERASE INHIBITOR/

Activating mutations of Ki-ras have been detected in most human pancre atic adenocarcinomas. Since Ras protein requires farnesylation to func tion, we investigated the effects of manumycin, a potent farnesyl:prot ein transferase inhibitor, on the growth in nude mice of a human pancr eatic cancer cell line, MIA PaCa-2, with a point mutation in the Ki-ra s gene. Tumor-bearing mice received intraperitoneal injection of 1 or 5 mg/kg manumycin daily for 5 days, or 2 mg/kg manumycin daily for 2 w eeks. Growth of inoculated tumors was significantly inhibited by the t reatment. The treatment significantly (P < 0.05) lowered the numbers o f bromodeoxyuridine-incorporating tumor cells. Manumycin did not have apparent hepatotoxicity in vivo. Farnesyl:protein transferase inhibito rs could offer a new approach for cancer chemotherapy.