Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor

Yoshifumi Matsui, Miyako Goto, Mayumi Iwakawa, Takehide Asano, Takashi Kenmochi, Takashi Imai, Takenori Ochiai

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1525-1528
Number of pages4
JournalOncology Reports
Volume10
Issue number5
Publication statusPublished - 01-09-2003

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Radiation Tolerance
Mitogen-Activated Protein Kinase Kinases
Transferases
Tumor Burden
Pancreatic Neoplasms
Heterografts
Growth
Proteins
Nude Mice
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
manumycin
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Matsui, Y., Goto, M., Iwakawa, M., Asano, T., Kenmochi, T., Imai, T., & Ochiai, T. (2003). Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor. Oncology Reports, 10(5), 1525-1528.
Matsui, Yoshifumi ; Goto, Miyako ; Iwakawa, Mayumi ; Asano, Takehide ; Kenmochi, Takashi ; Imai, Takashi ; Ochiai, Takenori. / Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor. In: Oncology Reports. 2003 ; Vol. 10, No. 5. pp. 1525-1528.
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abstract = "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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Matsui, Y, Goto, M, Iwakawa, M, Asano, T, Kenmochi, T, Imai, T & Ochiai, T 2003, 'Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor', Oncology Reports, vol. 10, no. 5, pp. 1525-1528.

Modified radiosensitivity of pancreatic cancer xenografts by farnesyl protein transferase inhibitor and MEK inhibitor. / Matsui, Yoshifumi; Goto, Miyako; Iwakawa, Mayumi; Asano, Takehide; Kenmochi, Takashi; Imai, Takashi; Ochiai, Takenori.

In: Oncology Reports, Vol. 10, No. 5, 01.09.2003, p. 1525-1528.

Research output: Contribution to journalArticle

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