TY - JOUR
T1 - Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor
AU - Matsui, Yoshifumi
AU - Goto, Miyako
AU - Iwakawa, Mayumi
AU - Asano, Takehide
AU - Kenmochi, Takashi
AU - Imai, Takashi
AU - Ochiai, Takenori
PY - 2003/9
Y1 - 2003/9
N2 - We investigated the effects of the farnesyl transferase inhibitor (FTI) manumycin and the MEK inhibitor PD98059 on growth of human pancreatic cancer, with mutant (SUIT2) or wild-type (BxPC-3) K-ras, xenografted into nude mice. Tumor growth was not reduced by either of the agents at a dose of 3 mg/kg without irradiation. Growth of SUIT2 irradiated at 15 Gy or 30 Gy was reduced by manumycin and PD98059: at 15 Gy, tumor volume doubling time (TVDT) increased from 18.6±3.8 to 36.3±14.2 days with PD98059 (p<0.05); at 30 Gy, TVDT increased from 32.8±6.8 to 70.5±10.5 days and 70.7±1.5 days, respectively. Manumycin tended to reduce growth of BxPC-3, but the difference in TVDT was not statistically significant. PD98059 significantly increased the TVDT of BxPC-3 at 30 Gy from 34.4±18 to 62.6±9.8 at 30 Gy. The present results suggest that Ras signaling pathways are potential targets for manipulation of radiosensitivity, and that induction of an alternative pathway may enhance radiosensitivity of pancreatic cancer.
AB - We investigated the effects of the farnesyl transferase inhibitor (FTI) manumycin and the MEK inhibitor PD98059 on growth of human pancreatic cancer, with mutant (SUIT2) or wild-type (BxPC-3) K-ras, xenografted into nude mice. Tumor growth was not reduced by either of the agents at a dose of 3 mg/kg without irradiation. Growth of SUIT2 irradiated at 15 Gy or 30 Gy was reduced by manumycin and PD98059: at 15 Gy, tumor volume doubling time (TVDT) increased from 18.6±3.8 to 36.3±14.2 days with PD98059 (p<0.05); at 30 Gy, TVDT increased from 32.8±6.8 to 70.5±10.5 days and 70.7±1.5 days, respectively. Manumycin tended to reduce growth of BxPC-3, but the difference in TVDT was not statistically significant. PD98059 significantly increased the TVDT of BxPC-3 at 30 Gy from 34.4±18 to 62.6±9.8 at 30 Gy. The present results suggest that Ras signaling pathways are potential targets for manipulation of radiosensitivity, and that induction of an alternative pathway may enhance radiosensitivity of pancreatic cancer.
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U2 - 10.3892/or.10.5.1525
DO - 10.3892/or.10.5.1525
M3 - Article
C2 - 12883735
AN - SCOPUS:2142686613
SN - 1021-335X
VL - 10
SP - 1525
EP - 1528
JO - Oncology reports
JF - Oncology reports
IS - 5
ER -
