Effect of Celecoxib and Novel Agent LC-1 in a Hamster Model of Lung Cancer

Reid C. Vegeler, Michele T. Yip-Schneider, Matthew Ralstin, Huangbing Wu, Peter A. Crooks, Sundar Neelakantan, Harikrishna Nakshatri, Christopher J. Sweeney, C. Max Schmidt

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4 Scopus citations

Abstract

Background: Lung cancer is the leading cause of cancer deaths in the United States. Inflammatory molecules, cyclooxygenase-2 (COX-2) and nuclear factor kappa B (NF-κB) have been implicated in lung carcinogenesis. The therapeutic potential of celecoxib, a COX-2 selective inhibitor, and LC-1, a pro-apoptotic drug with accompanying inhibition of NF-κB, were investigated. Materials and methods: Syrian golden hamsters (n = 140) underwent N-nitroso-bis(2-oxopropyl)amine (BOP) injection weekly for 6 wk. Hamsters were randomized into seven groups: placebo and low/high doses of LC-1, celecoxib, and LC-1/celecoxib. Treatments were given via orogastric lavage for 32 wk. Immunohistochemistry was used to determine COX-2 expression and NF-κB activity. Ki-67 labeling was used as an index of proliferation. COX activity was measured by prostaglandin E2 enzyme-linked immunosorbent assay. Results: BOP successfully induced lung adenocarcinoma in 63% of placebo animals. Lung tumors strongly expressed COX-2 and NF-κB. Prostaglandin E2 levels were decreased in celecoxib compared with placebo groups (P < 0.05) reflecting suppression of COX activity, but no decrease in NF-κB was seen as measured by immunohistochemistry in the tumors. There was no significant difference in tumor size, tumor incidence, or tumor proliferation index between placebo and treatment groups. Conclusions: Carcinogen exposure results in increased COX-2 and NF-κB expression and suggests a role in carcinogenesis. Celecoxib and LC-1 did not have any effect in preventing lung cancer development when co-administered with and continued after the carcinogen BOP. Higher doses that can result in suppression of NF-κB activity will need to be explored to determine the viability of this approach to prevent lung cancer development.

Original languageEnglish (US)
Pages (from-to)169-176
Number of pages8
JournalJournal of Surgical Research
Volume143
Issue number1
DOIs
StatePublished - Nov 1 2007

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Keywords

  • celecoxib
  • cyclooxygenase (COX)
  • lung cancer
  • nuclear factor kappa B (NF-κB)
  • parthenolide

ASJC Scopus subject areas

  • Surgery

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