A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras- transformed rat intestinal epithelial cells

G. G. Sheng, J. Shao, H. Sheng, E. B. Hooton, P. C. Isakson, J. D. Morrow, Jr Coffey R.J., R. N. DuBois, R. D. Beauchamp

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Abstract

Background and Aims: Constitutive expression of cyclooxygenase 2 (COX- 2) has been found in 85% of colorectal cancers. Ras mutations are found in 50% of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells. Methods: Cell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis. Results: The expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC- 58125 treatment reduced the colony formation in Matrigel by 83.0%. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3% in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation. Conclusions: Overexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis.

Original languageEnglish (US)
Pages (from-to)1883-1891
Number of pages9
JournalGastroenterology
Volume113
Issue number6
StatePublished - 1997
Externally publishedYes

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Cyclooxygenase 2 Inhibitors
Epithelial Cells
Growth
Nude Mice
Apoptosis
DNA Fragmentation
Subcutaneous Tissue
Epoprostenol
Cyclooxygenase 2
Colorectal Neoplasms
Adenocarcinoma
Cell Count
Cell Proliferation
Messenger RNA
Mutation
1-((4-methylsulfonyl)phenyl)-3-trifluoromethyl-5-(4-fluorophenyl)pyrazole
Serum

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Sheng, G. G., Shao, J., Sheng, H., Hooton, E. B., Isakson, P. C., Morrow, J. D., ... Beauchamp, R. D. (1997). A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras- transformed rat intestinal epithelial cells. Gastroenterology, 113(6), 1883-1891.

A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras- transformed rat intestinal epithelial cells. / Sheng, G. G.; Shao, J.; Sheng, H.; Hooton, E. B.; Isakson, P. C.; Morrow, J. D.; Coffey R.J., Jr; DuBois, R. N.; Beauchamp, R. D.

In: Gastroenterology, Vol. 113, No. 6, 1997, p. 1883-1891.

Research output: Contribution to journalArticle

Sheng, GG, Shao, J, Sheng, H, Hooton, EB, Isakson, PC, Morrow, JD, Coffey R.J., J, DuBois, RN & Beauchamp, RD 1997, 'A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras- transformed rat intestinal epithelial cells', Gastroenterology, vol. 113, no. 6, pp. 1883-1891.
Sheng GG, Shao J, Sheng H, Hooton EB, Isakson PC, Morrow JD et al. A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras- transformed rat intestinal epithelial cells. Gastroenterology. 1997;113(6):1883-1891.
Sheng, G. G. ; Shao, J. ; Sheng, H. ; Hooton, E. B. ; Isakson, P. C. ; Morrow, J. D. ; Coffey R.J., Jr ; DuBois, R. N. ; Beauchamp, R. D. / A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras- transformed rat intestinal epithelial cells. In: Gastroenterology. 1997 ; Vol. 113, No. 6. pp. 1883-1891.
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title = "A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras- transformed rat intestinal epithelial cells",
abstract = "Background and Aims: Constitutive expression of cyclooxygenase 2 (COX- 2) has been found in 85{\%} of colorectal cancers. Ras mutations are found in 50{\%} of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells. Methods: Cell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis. Results: The expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC- 58125 treatment reduced the colony formation in Matrigel by 83.0{\%}. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3{\%} in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation. Conclusions: Overexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis.",
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T1 - A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras- transformed rat intestinal epithelial cells

AU - Sheng, G. G.

AU - Shao, J.

AU - Sheng, H.

AU - Hooton, E. B.

AU - Isakson, P. C.

AU - Morrow, J. D.

AU - Coffey R.J., Jr

AU - DuBois, R. N.

AU - Beauchamp, R. D.

PY - 1997

Y1 - 1997

N2 - Background and Aims: Constitutive expression of cyclooxygenase 2 (COX- 2) has been found in 85% of colorectal cancers. Ras mutations are found in 50% of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells. Methods: Cell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis. Results: The expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC- 58125 treatment reduced the colony formation in Matrigel by 83.0%. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3% in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation. Conclusions: Overexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis.

AB - Background and Aims: Constitutive expression of cyclooxygenase 2 (COX- 2) has been found in 85% of colorectal cancers. Ras mutations are found in 50% of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells. Methods: Cell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis. Results: The expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC- 58125 treatment reduced the colony formation in Matrigel by 83.0%. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3% in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation. Conclusions: Overexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis.

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