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Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels.
Cancer Res. 2005 Oct 15; 65(20):9501-9.CR

Abstract

To characterize the radiation-enhancing effects on human cancer cells and underlying mechanisms of celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, and to ascertain whether its effects are COX-2 dependent. Clonogenic cytotoxicity assays and radiation survival assays after treatment with celecoxib +/- radiation were done on four human cancer cell lines that expressed differential COX-2 levels. Stably COX-2 knocked down or overexpressed cell lines were developed, and clonogenic assays, apoptosis assays, or cell cycle change measurements were conducted after treatment with celecoxib +/- radiation. Prostaglandin E(2) (PGE2) was applied to medium after treatment with celecoxib +/- radiation to determine whether the radiation-enhancing effect associated with celecoxib results from reduced generation of prostaglandin. Celecoxib's radiation-enhancing effect was observed in COX-2-expressing A549 and NCI-H460 cells but was not observed in the COX-2 nonexpressing MCF-7 and HCT-116 cells. Celecoxib's radiation-enhancing effects in A549 cells were shown to disappear after the administration of COX-2 knocked down. In contrast, the HCT-116 cells were radiosensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE2 after treatment with celecoxib +/- radiation had no significant effects on celecoxib's radiation-enhancing effects in A549 and COX-2 transfected HCT-116 cells. Radiation-induced G2-M arrest was enhanced and sustained in the COX-2-overexpressing cells compared with that seen in COX-2 low-expressing cells. Celecoxib or NS-398 effected no changes or attenuated radiation-induced G(2)-M arrest in the COX-2-overexpressing cells but further enhanced the radiation-induced G(2)-M arrest in the COX-2 low-expressing cells. Celecoxib's radiation-enhancing effects seem to occur in a COX-2 expression-dependent manner in the cancer cells. This effect does not seem to be the result of reduced PGE2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G2-M arrest in the COX-2-overexpressing cells, which may allow the arrested cells to enter mitosis and die after radiation, but may also further enhance radiation-induced G2-M arrest in the COX-2 low-expressing cells, by virtue of another mechanism.

Authors+Show Affiliations

Yonsei Institute for Cancer Research, Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, South Korea .No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16230415

Citation

Shin, You Keun, et al. "Radiosensitivity Enhancement By Celecoxib, a Cyclooxygenase (COX)-2 Selective Inhibitor, Via COX-2-dependent Cell Cycle Regulation On Human Cancer Cells Expressing Differential COX-2 Levels." Cancer Research, vol. 65, no. 20, 2005, pp. 9501-9.
Shin YK, Park JS, Kim HS, et al. Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels. Cancer Res. 2005;65(20):9501-9.
Shin, Y. K., Park, J. S., Kim, H. S., Jun, H. J., Kim, G. E., Suh, C. O., Yun, Y. S., & Pyo, H. (2005). Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels. Cancer Research, 65(20), 9501-9.
Shin YK, et al. Radiosensitivity Enhancement By Celecoxib, a Cyclooxygenase (COX)-2 Selective Inhibitor, Via COX-2-dependent Cell Cycle Regulation On Human Cancer Cells Expressing Differential COX-2 Levels. Cancer Res. 2005 Oct 15;65(20):9501-9. PubMed PMID: 16230415.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Radiosensitivity enhancement by celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, via COX-2-dependent cell cycle regulation on human cancer cells expressing differential COX-2 levels. AU - Shin,You Keun, AU - Park,Ji Sun, AU - Kim,Hyun Seok, AU - Jun,Hyun Jung, AU - Kim,Gwi Eon, AU - Suh,Chang Ok, AU - Yun,Yeon Sook, AU - Pyo,Hongryull, PY - 2005/10/19/pubmed PY - 2005/12/20/medline PY - 2005/10/19/entrez SP - 9501 EP - 9 JF - Cancer research JO - Cancer Res VL - 65 IS - 20 N2 - To characterize the radiation-enhancing effects on human cancer cells and underlying mechanisms of celecoxib, a cyclooxygenase (COX)-2 selective inhibitor, and to ascertain whether its effects are COX-2 dependent. Clonogenic cytotoxicity assays and radiation survival assays after treatment with celecoxib +/- radiation were done on four human cancer cell lines that expressed differential COX-2 levels. Stably COX-2 knocked down or overexpressed cell lines were developed, and clonogenic assays, apoptosis assays, or cell cycle change measurements were conducted after treatment with celecoxib +/- radiation. Prostaglandin E(2) (PGE2) was applied to medium after treatment with celecoxib +/- radiation to determine whether the radiation-enhancing effect associated with celecoxib results from reduced generation of prostaglandin. Celecoxib's radiation-enhancing effect was observed in COX-2-expressing A549 and NCI-H460 cells but was not observed in the COX-2 nonexpressing MCF-7 and HCT-116 cells. Celecoxib's radiation-enhancing effects in A549 cells were shown to disappear after the administration of COX-2 knocked down. In contrast, the HCT-116 cells were radiosensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE2 after treatment with celecoxib +/- radiation had no significant effects on celecoxib's radiation-enhancing effects in A549 and COX-2 transfected HCT-116 cells. Radiation-induced G2-M arrest was enhanced and sustained in the COX-2-overexpressing cells compared with that seen in COX-2 low-expressing cells. Celecoxib or NS-398 effected no changes or attenuated radiation-induced G(2)-M arrest in the COX-2-overexpressing cells but further enhanced the radiation-induced G(2)-M arrest in the COX-2 low-expressing cells. Celecoxib's radiation-enhancing effects seem to occur in a COX-2 expression-dependent manner in the cancer cells. This effect does not seem to be the result of reduced PGE2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G2-M arrest in the COX-2-overexpressing cells, which may allow the arrested cells to enter mitosis and die after radiation, but may also further enhance radiation-induced G2-M arrest in the COX-2 low-expressing cells, by virtue of another mechanism. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/16230415/Radiosensitivity_enhancement_by_celecoxib_a_cyclooxygenase__COX__2_selective_inhibitor_via_COX_2_dependent_cell_cycle_regulation_on_human_cancer_cells_expressing_differential_COX_2_levels_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16230415 DB - PRIME DP - Unbound Medicine ER -