Suppressive effect of CPT-11 on rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine

  • Authors:
    • Yushi Fukiwara
    • Harushi Osugi
    • Keichirou Morimura
    • Masashi Takemura
    • Shigeru Lee
    • Kazuhiro Hirohashi
    • Shoji Fukushima
    • Shigefumi Suehiro
  • View Affiliations

  • Published online on: December 1, 2004     https://doi.org/10.3892/or.12.6.1169
  • Pages: 1169-1176
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Abstract

Irinotecan hydrochloride (CPT-11) is a potent anti-cancer drug with suppressive effects against gastric and colorectal cancers. However, no evaluation of CPT-11 for esophageal squamous cell carcinoma has been performed in vivo. In this study, we examined the tumor suppressive effects of CPT-11 on N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. One hundred and fourteen rats were divided into six groups. Rats in groups 1-5 were treated with subcutaneous injection of NMBA at a dose of 0.5 mg/kg 3 times per week for 5 weeks. Rats in group 6 served as a control. Rats in groups 2 and 3 were treated with intragastric (i.g.) administration of CPT-11 at doses of 20 and 40 mg/kg, respectively, once a week simultaneously with NMBA-initiation up to the end of the experiment. Rats in groups 4 and 5 were treated with i.g. administration of CPT-11 at doses of 20 and 40 mg/kg, respectively, once a week after the NMBA-initiation period up to the end of the experiment. The incidence of papilloma and hyperplasia in the esophagus showed no difference between NMBA-treated groups. However, the multiplicity of hyperplasia was significantly reduced in all CPT-11 administration groups. Immunohistochemically, expression of proliferating cell nuclear antigen (PCNA) was decreased on carcinogen-exposed squamous epithelium and preneoplastic lesions, although no significant differences were detected in the expression of single-strand DNA (ssDNA) and p53. These data suggest that CPT-11 has suppressive effects for esophageal tumors in the early step of the multistep process of carcinogenesis through antiproliferative mechanism.

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December 2004
Volume 12 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Fukiwara Y, Osugi H, Morimura K, Takemura M, Lee S, Hirohashi K, Fukushima S and Suehiro S: Suppressive effect of CPT-11 on rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine. Oncol Rep 12: 1169-1176, 2004
APA
Fukiwara, Y., Osugi, H., Morimura, K., Takemura, M., Lee, S., Hirohashi, K. ... Suehiro, S. (2004). Suppressive effect of CPT-11 on rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine. Oncology Reports, 12, 1169-1176. https://doi.org/10.3892/or.12.6.1169
MLA
Fukiwara, Y., Osugi, H., Morimura, K., Takemura, M., Lee, S., Hirohashi, K., Fukushima, S., Suehiro, S."Suppressive effect of CPT-11 on rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine". Oncology Reports 12.6 (2004): 1169-1176.
Chicago
Fukiwara, Y., Osugi, H., Morimura, K., Takemura, M., Lee, S., Hirohashi, K., Fukushima, S., Suehiro, S."Suppressive effect of CPT-11 on rat esophageal tumorigenesis induced by N-nitrosomethylbenzylamine". Oncology Reports 12, no. 6 (2004): 1169-1176. https://doi.org/10.3892/or.12.6.1169