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

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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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

Fingerprint

Celecoxib
NF-kappa B
Cricetinae
Lung Neoplasms
Cyclooxygenase 2
Placebos
Neoplasms
Dinoprostone
Carcinogens
Carcinogenesis
Immunohistochemistry
Lung
Cyclooxygenase 2 Inhibitors
Therapeutic Irrigation
Mesocricetus
Prodrugs
Amines
Cause of Death
Therapeutics
Enzyme-Linked Immunosorbent Assay

Keywords

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

ASJC Scopus subject areas

  • Surgery

Cite this

Effect of Celecoxib and Novel Agent LC-1 in a Hamster Model of Lung Cancer. / Vegeler, Reid C.; Yip-Schneider, Michele; Ralstin, Matthew; Wu, Huangbing; Crooks, Peter A.; Neelakantan, Sundar; Nakshatri, Harikrishna; Sweeney, Christopher J.; Schmidt, C.

In: Journal of Surgical Research, Vol. 143, No. 1, 11.2007, p. 169-176.

Research output: Contribution to journalArticle

Vegeler, Reid C. ; Yip-Schneider, Michele ; Ralstin, Matthew ; Wu, Huangbing ; Crooks, Peter A. ; Neelakantan, Sundar ; Nakshatri, Harikrishna ; Sweeney, Christopher J. ; Schmidt, C. / Effect of Celecoxib and Novel Agent LC-1 in a Hamster Model of Lung Cancer. In: Journal of Surgical Research. 2007 ; Vol. 143, No. 1. pp. 169-176.
@article{083e0e2df62e4cdeb5ca2446fcbe6a00,
title = "Effect of Celecoxib and Novel Agent LC-1 in a Hamster Model of Lung Cancer",
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.",
keywords = "celecoxib, cyclooxygenase (COX), lung cancer, nuclear factor kappa B (NF-κB), parthenolide",
author = "Vegeler, {Reid C.} and Michele Yip-Schneider and Matthew Ralstin and Huangbing Wu and Crooks, {Peter A.} and Sundar Neelakantan and Harikrishna Nakshatri and Sweeney, {Christopher J.} and C. Schmidt",
year = "2007",
month = "11",
doi = "10.1016/j.jss.2007.08.007",
language = "English",
volume = "143",
pages = "169--176",
journal = "Journal of Surgical Research",
issn = "0022-4804",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Effect of Celecoxib and Novel Agent LC-1 in a Hamster Model of Lung Cancer

AU - Vegeler, Reid C.

AU - Yip-Schneider, Michele

AU - Ralstin, Matthew

AU - Wu, Huangbing

AU - Crooks, Peter A.

AU - Neelakantan, Sundar

AU - Nakshatri, Harikrishna

AU - Sweeney, Christopher J.

AU - Schmidt, C.

PY - 2007/11

Y1 - 2007/11

N2 - 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.

AB - 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.

KW - celecoxib

KW - cyclooxygenase (COX)

KW - lung cancer

KW - nuclear factor kappa B (NF-κB)

KW - parthenolide

UR - http://www.scopus.com/inward/record.url?scp=35248885740&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=35248885740&partnerID=8YFLogxK

U2 - 10.1016/j.jss.2007.08.007

DO - 10.1016/j.jss.2007.08.007

M3 - Article

C2 - 17950089

AN - SCOPUS:35248885740

VL - 143

SP - 169

EP - 176

JO - Journal of Surgical Research

JF - Journal of Surgical Research

SN - 0022-4804

IS - 1

ER -