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

You Keun Shin, Ji Sun Park, Hyun Seok Kim, Hyun Jung Jun, Gwi Eon Kim, Chang Ok Suh, Yeon Sook Yun, Hongryull Pyo

Research output: Contribution to journalArticle

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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 (PGE 2) 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 radio-sensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE 2 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 G 2-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 PGE 2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G 2-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 G 2-M arrest in the COX-2 low-expressing cells, by virtue of another mechanism.

Original languageEnglish
Pages (from-to)9501-9509
Number of pages9
JournalCancer Research
Volume65
Issue number20
DOIs
Publication statusPublished - 2005 Oct 15

Fingerprint

Celecoxib
Cyclooxygenase 2 Inhibitors
Radiation Tolerance
Cyclooxygenase 2
Cell Cycle
Radiation
Radiation Effects
Neoplasms
HCT116 Cells
Prostaglandins E

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Shin, You Keun ; Park, Ji Sun ; Kim, Hyun Seok ; Jun, Hyun Jung ; Kim, Gwi Eon ; Suh, Chang Ok ; Yun, Yeon Sook ; Pyo, Hongryull. / 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. In: Cancer Research. 2005 ; Vol. 65, No. 20. pp. 9501-9509.
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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 (PGE 2) 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 radio-sensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE 2 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 G 2-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 PGE 2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G 2-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 G 2-M arrest in the COX-2 low-expressing cells, by virtue of another mechanism.",
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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. / Shin, You Keun; Park, Ji Sun; Kim, Hyun Seok; Jun, Hyun Jung; Kim, Gwi Eon; Suh, Chang Ok; Yun, Yeon Sook; Pyo, Hongryull.

In: Cancer Research, Vol. 65, No. 20, 15.10.2005, p. 9501-9509.

Research output: Contribution to journalArticle

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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 (PGE 2) 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 radio-sensitized by celecoxib after being transfected with COX-2 expression vector. The addition of PGE 2 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 G 2-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 PGE 2 generation. Celecoxib may exert an inhibitory effect on enhanced radiation-induced G 2-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 G 2-M arrest in the COX-2 low-expressing cells, by virtue of another mechanism.

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