in vitro synergistic antitumor activity of a combination of 5-fluorouracil and irinotecan in human colon cancer

  • Authors:
    • Yasuhiro Inoue
    • Koji Tanaka
    • Junichiro Hiro
    • Shigeyuki Yoshiyama
    • Yuji Toiyama
    • Tomoya Eguchi
    • Chikao Miki
    • Masato Kusunoki
  • View Affiliations

  • Published online on: February 1, 2006     https://doi.org/10.3892/ijo.28.2.479
  • Pages: 479-486
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Abstract

The combination of irinotecan and a fluoro-pyrimidine is widely accepted as a treatment for advanced colorectal cancer. However, evaluable data on the feasibility of these combinations has not been presented, and an optimal sequence for administration has not been experimentally and clinically determined. The sequential effect of a combination of 5-FU and CPT-11 in the human colon cancer cell line LoVo was evaluated by WST-8 colorimetric assay. The cytotoxicy and cell cycle distributions of each drug were analyzed by apoptosis assay and flow cytometry. Further, the potential mechanisms of the sequence-dependent effects were investigated by a microarray technique, and confirmed by Western blot analysis. The cytotoxicity of 5-FU (10, 100, 1000 µM) followed by CPT-11 (1 µM) was significantly greater than that of CPT-11 (1 µM) followed by 5-FU (10, 100, 1000 µM) (p<0.05). In cell cycle distribution, 5-FU exposure for 24 h increased the S phase fraction in a dose- dependent manner; though there was no significant difference in cell cycle distribution in 24 h CPT-11 (0.01-1 µM) exposure. Microarray analysis revealed that expressions of some apoptosis related genes such as Bcl-2 changed, and were correlated with sequence-dependent cytotoxicity of the 5-FU↷CPT-11 sequence. Western blot analysis confirmed that the Bcl-2/Bax ratio was lower after 5-FU↷CPT-11 sequence than before. The sequence-dependent cytotoxic effect may depend on the sensitizing effect of 5-FU pretreatment on CPT-11 cytotoxicity. 5-FU followed by CPT-11 administration may be an optimal sequence for IFL treatment of advanced colon cancer.

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February 2006
Volume 28 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Inoue Y, Tanaka K, Hiro J, Yoshiyama S, Toiyama Y, Eguchi T, Miki C and Kusunoki M: in vitro synergistic antitumor activity of a combination of 5-fluorouracil and irinotecan in human colon cancer. Int J Oncol 28: 479-486, 2006
APA
Inoue, Y., Tanaka, K., Hiro, J., Yoshiyama, S., Toiyama, Y., Eguchi, T. ... Kusunoki, M. (2006). in vitro synergistic antitumor activity of a combination of 5-fluorouracil and irinotecan in human colon cancer. International Journal of Oncology, 28, 479-486. https://doi.org/10.3892/ijo.28.2.479
MLA
Inoue, Y., Tanaka, K., Hiro, J., Yoshiyama, S., Toiyama, Y., Eguchi, T., Miki, C., Kusunoki, M."in vitro synergistic antitumor activity of a combination of 5-fluorouracil and irinotecan in human colon cancer". International Journal of Oncology 28.2 (2006): 479-486.
Chicago
Inoue, Y., Tanaka, K., Hiro, J., Yoshiyama, S., Toiyama, Y., Eguchi, T., Miki, C., Kusunoki, M."in vitro synergistic antitumor activity of a combination of 5-fluorouracil and irinotecan in human colon cancer". International Journal of Oncology 28, no. 2 (2006): 479-486. https://doi.org/10.3892/ijo.28.2.479