TY - JOUR
T1 - Inhibition of growth and invasive activity of human pancreatic cancer cells by a farnesyltransferase inhibitor, manumycin
AU - Kainuma, Osamu
AU - Asano, Takehide
AU - Hasegawa, Masayuki
AU - Kenmochi, Takashi
AU - Nakagohri, Toshio
AU - Tokoro, Yoshiharu
AU - Isono, Kaichi
PY - 1997/11
Y1 - 1997/11
N2 - The effects of manumycin, a competitive farnesyltransferase (FTase) inhibitor, on pancreatic cancer cell lines with or without K-ras mutation were studied. Manumycin inhibited the growth of human pancreatic cancer cells (SUIT-2, MIA PaCa-2, AsPC-1, BxPC-3) in a close-dependent manner. The 50% inhibitory concentration (IC50) in cell lines with a mutant K-ras gene (SUIT-2, MIA PaCa-2, AsPC-1) was lower than that in BxPC-3 with a wild-type ras. Both mitogen-activated protein kinase activity after growth stimuli and the ability for chemotactic invasion were markedly more inhibited by manumycin in SUIT-2 than in BxPC-3. These results suggest that mutated Ras is more sensitive to manumycin than the wild type. Furthermore, tumor growth and liver metastasis in nude mice inoculated with manumycin-treated SUIT-2 cells were inhibited close dependently. Inhibition of Ras activity might be a new anticancer strategy in pancreatic cancer in which Ras plays a role.
AB - The effects of manumycin, a competitive farnesyltransferase (FTase) inhibitor, on pancreatic cancer cell lines with or without K-ras mutation were studied. Manumycin inhibited the growth of human pancreatic cancer cells (SUIT-2, MIA PaCa-2, AsPC-1, BxPC-3) in a close-dependent manner. The 50% inhibitory concentration (IC50) in cell lines with a mutant K-ras gene (SUIT-2, MIA PaCa-2, AsPC-1) was lower than that in BxPC-3 with a wild-type ras. Both mitogen-activated protein kinase activity after growth stimuli and the ability for chemotactic invasion were markedly more inhibited by manumycin in SUIT-2 than in BxPC-3. These results suggest that mutated Ras is more sensitive to manumycin than the wild type. Furthermore, tumor growth and liver metastasis in nude mice inoculated with manumycin-treated SUIT-2 cells were inhibited close dependently. Inhibition of Ras activity might be a new anticancer strategy in pancreatic cancer in which Ras plays a role.
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U2 - 10.1097/00006676-199711000-00008
DO - 10.1097/00006676-199711000-00008
M3 - Article
C2 - 9361092
AN - SCOPUS:0030733653
SN - 0885-3177
VL - 15
SP - 379
EP - 383
JO - Pancreas
JF - Pancreas
IS - 4
ER -
