Celecoxib prevents tumor growth in vivo without toxicity to normal gut

Lack of correlation between in vitro and in vivo models

C. S. Williams, A. J M Watson, H. Sheng, R. Helou, J. Shao, R. N. DuBois

Research output: Contribution to journalArticle

303 Citations (Scopus)

Abstract

Nonsteroidal anti-inflammatory drugs have potential for use in the prevention and/or treatment of colorectal cancer. We have studied the cytotoxic effect of a specific COX-2 inhibitor, celecoxib, against LLC, HCA-7, and HCT-15 cells grown in cell culture and have compared these results with its effect on HCA-7 cells grown as xenografts in nude mice. 'High-dose' celecoxib (>20 μM) reduced the viability of all three cell lines in vitro as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Flow cytometric analysis demonstrated that this loss of viability was attributable to the induction of apoptosis. Significantly, concentrations of the drug <10 μM had no effect on cell viability in vitro. The cytotoxic effects of high-dose celecoxib were independent of COX-2 inhibition because similar effects were observed in cox-2 (+/+), cox-2 (+/-) and cox-2 (-/-) fibroblasts. A plasma concentration of 2.3 ± 0.7 μM was achieved when celecoxib (1250 mg/kg of chow) was fed to animals ad libitum. Despite a lack of toxicity at 2-3 μM celecoxib in vitro, there was attenuation of HCA-7 xenograft growth in vivo. Celecoxib had no effect on apoptosis, cell division, or the epithelial architecture of the normal gut in treated mice. These results support the need for additional clinical evaluation of celecoxib for treatment and/or prevention of colorectal cancer in humans.

Original languageEnglish (US)
Pages (from-to)6045-6051
Number of pages7
JournalCancer Research
Volume60
Issue number21
StatePublished - Nov 1 2000
Externally publishedYes

Fingerprint

Celecoxib
Growth
Neoplasms
Heterografts
Colorectal Neoplasms
Apoptosis
Cyclooxygenase 2 Inhibitors
In Vitro Techniques
Nude Mice
Pharmaceutical Preparations
Cell Division
Cell Survival
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Williams, C. S., Watson, A. J. M., Sheng, H., Helou, R., Shao, J., & DuBois, R. N. (2000). Celecoxib prevents tumor growth in vivo without toxicity to normal gut: Lack of correlation between in vitro and in vivo models. Cancer Research, 60(21), 6045-6051.

Celecoxib prevents tumor growth in vivo without toxicity to normal gut : Lack of correlation between in vitro and in vivo models. / Williams, C. S.; Watson, A. J M; Sheng, H.; Helou, R.; Shao, J.; DuBois, R. N.

In: Cancer Research, Vol. 60, No. 21, 01.11.2000, p. 6045-6051.

Research output: Contribution to journalArticle

Williams, CS, Watson, AJM, Sheng, H, Helou, R, Shao, J & DuBois, RN 2000, 'Celecoxib prevents tumor growth in vivo without toxicity to normal gut: Lack of correlation between in vitro and in vivo models', Cancer Research, vol. 60, no. 21, pp. 6045-6051.
Williams, C. S. ; Watson, A. J M ; Sheng, H. ; Helou, R. ; Shao, J. ; DuBois, R. N. / Celecoxib prevents tumor growth in vivo without toxicity to normal gut : Lack of correlation between in vitro and in vivo models. In: Cancer Research. 2000 ; Vol. 60, No. 21. pp. 6045-6051.
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