Suppression of Human Pancreatic Cancer Growth in BALB/c Nude Mice by Manumycin, a Farnesyl:protein Transferase Inhibitor

• Published in: Cancer science 1996-02, Vol.87 (2), p.113-116
• Main Authors: Ito, Toshio, Kawata, Sumio, Tamura, Shinji, Igura, Takumi, Nagase, Toshihiko, Miyagawa, Jun‐ichiro, Yamazaki, Eiji, Ishiguro, Hiroshi, Matsuzawa, Yuji
• Format: Article
• Language: English
• Subjects: Alkyl and Aryl Transferases; Animals; Antineoplastic agents; Antineoplastic Agents - therapeutic use; Aquatic life; Biological and medical sciences; Bromodeoxyuridine; Chemotherapy; DNA, Neoplasm - biosynthesis; Dose-Response Relationship, Drug; Enzyme Inhibitors - therapeutic use; Farnesyl:protein transferase inhibitor; Farnesyltranstransferase; Hepatotoxicity; Humans; Invertebrates; Male; Manumycin; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Mutation; Neoplasm Transplantation; Nude mouse; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pharmacology. Drug treatments; Point mutation; Polyenes - therapeutic use; Polyunsaturated Alkamides; Proteins; Rapid Communication; Ras; Ras protein; Transferases - antagonists & inhibitors; Transplantation, Heterologous; Tumor cells; Tumors
• ISSN: 0910-5050; 1347-9032; 1349-7006; 1876-4673
• DOI: 10.1111/j.1349-7006.1996.tb03146.x

Activating mutations of Ki‐ras have been detected in most human pancreatic adenocarcinomas. Since Ras protein requires farnesylation to function, we investigated the effects of manumycin, a potent farnesyl:protein transferase inhibitor, on the growth in nude mice of a human pancreatic cancer cell line, MIA PaCa‐2, with a point mutation in the Ki‐ras 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 weeks. Growth of inoculated tumors was significantly inhibited by the treatment. The treatment significantly (P