Suppression of human pancreatic cancer growth in BALB/c nude mice by manumycin, a farnesyl:protein transferase inhibitor

被引：54

作者：

Ito, T ^{[1
]}

Kawata, S ^{[1
]}

Tamura, S ^{[1
]}

Igura, T ^{[1
]}

Nagase, T ^{[1
]}

Miyagawa, J ^{[1
]}

Yamazaki, E ^{[1
]}

Ishiguro, H ^{[1
]}

Matsuzawa, Y ^{[1
]}

机构：

[1] OSAKA UNIV,SCH MED,DEPT INTERNAL MED 2,SUITA,OSAKA 565,JAPAN

来源：

JAPANESE JOURNAL OF CANCER RESEARCH | 1996年 / 87卷 / 02期

关键词：

farnesyl:protein transferase inhibitor; manumycin; pancreatic cancer; nude mouse; Ras;

D O I：

10.1111/j.1349-7006.1996.tb03146.x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 < 0.05) lowered the numbers of bromodeoxyuridine-incorporating tumor cells. Manumycin did not have apparent hepatotoxicity in vivo. Farnesyl:protein transferase inhibitors could offer a new approach for cancer chemotherapy.

引用

页码：113 / 116

页数：4

共 15 条

[1] RAS GENES [J].

BARBACID, M .

ANNUAL REVIEW OF BIOCHEMISTRY, 1987, 56 :779-827

[2]

DER CJ, 1991, CANCER CELL-MON REV, V3, P331

[3] RAS C-TERMINAL PROCESSING ENZYMES - MINIREVIEW NEW DRUG TARGETS [J].

GIBBS, JB .

CELL, 1991, 65 (01) :1-4

[4]

GIBBS JB, 1993, J BIOL CHEM, V268, P7617

[5] IDENTIFICATION OF RAS FARNESYLTRANSFERASE INHIBITORS BY MICROBIAL SCREENING [J].

HARA, M ;

AKASAKA, K ;

AKINAGA, S ;

OKABE, M ;

NAKANO, H ;

GOMEZ, R ;

WOOD, D ;

UH, M ;

TAMANOI, F .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (06) :2281-2285

[6] BENZODIAZEPINE PEPTIDOMIMETICS - POTENT INHIBITORS OF RAS FARNESYLATION IN ANIMAL-CELLS [J].

JAMES, GL ;

GOLDSTEIN, JL ;

BROWN, MS ;

RAWSON, TE ;

SOMERS, TC ;

MCDOWELL, RS ;

CROWLEY, CW ;

LUCAS, BK ;

LEVINSON, AD ;

MARSTERS, JC .

SCIENCE, 1993, 260 (5116) :1937-1942

[7] MODULATION OF THE MEVALONATE PATHWAY AND CELL-GROWTH BY PRAVASTATIN AND D-LIMONENE IN A HUMAN HEPATOMA-CELL LINE (HEP G2) [J].

KAWATA, S ;

NAGASE, T ;

YAMASAKI, E ;

ISHIGURO, H ;

MATSUZAWA, Y .

BRITISH JOURNAL OF CANCER, 1994, 69 (06) :1015-1020

[8] EFFECT OF PRAVASTATIN, A POTENT 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE INHIBITOR, ON SURVIVAL OF AH130 HEPATOMA-BEARING RATS [J].

KAWATA, S ;

KAKIMOTO, H ;

ISHIGURO, H ;

YAMASAKI, E ;

INUI, Y ;

MATSUZAWA, Y .

JAPANESE JOURNAL OF CANCER RESEARCH, 1992, 83 (11) :1120-1123

[9] SELECTIVE-INHIBITION OF RAS-DEPENDENT TRANSFORMATION BY A FARNESYLTRANSFERASE INHIBITOR [J].

KOHL, NE ;

MOSSER, SD ;

DESOLMS, SJ ;

GIULIANI, EA ;

POMPLIANO, DL ;

GRAHAM, SL ;

SMITH, RL ;

SCOLNICK, EM ;

OLIFF, A ;

GIBBS, JB .

SCIENCE, 1993, 260 (5116) :1934-1937

[10] PEPTICINNAMINS, NEW FARNESYL-PROTEIN TRANSFERASE INHIBITORS PRODUCED BY AN ACTINOMYCETE .1. PRODUCING STRAIN, FERMENTATION, ISOLATION AND BIOLOGICAL-ACTIVITY [J].

OMURA, S ;

VANDERPYL, D ;

INOKOSHI, J ;

TAKAHASHI, Y ;

TAKESHIMA, H .

JOURNAL OF ANTIBIOTICS, 1993, 46 (02) :222-228

← 1 2 →