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Titolo:
A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxygenase-2
Autore:
Pyo, H; Choy, H; Amorino, GP; Kim, JS; Cao, QW; Hercules, SK; DuBois, RN;
Indirizzi:
Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 iat Oncol, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Dept Med, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Dept Cell Biol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Cell Biol, Nashville, TN 37232 USA
Titolo Testata:
CLINICAL CANCER RESEARCH
fascicolo: 10, volume: 7, anno: 2001,
pagine: 2998 - 3005
SICI:
1078-0432(200110)7:10<2998:ASCINE>2.0.ZU;2-F
Fonte:
ISI
Lingua:
ENG
Soggetto:
COLON-CANCER CELLS; NONSTEROIDAL ANTIINFLAMMATORY DRUG; HUMAN COLORECTAL-CANCER; TUMOR RADIORESPONSE; INDUCED APOPTOSIS; EPITHELIAL-CELLS; BCL-2 EXPRESSION; CARCINOMA-CELLS; COX-2 PROTEIN; MURINE TUMORS;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Choy, H Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, B902 TVC,22nd Ave & Pierce, Nashville, TN 37232 USA Vanderbilt Univ B902 TVC,22nd Ave & Pierce Nashville TN USA 37232
Citazione:
H. Pyo et al., "A selective cyclooxygenase-2 inhibitor, NS-398, enhances the effect of radiation in vitro and in vivo preferentially on the cells that express cyclooxygenase-2", CLIN CANC R, 7(10), 2001, pp. 2998-3005

Abstract

It has been proposed that Cyclooxygenase (COX)-2 inhibitors may be able toenhance the effects of chemotherapeutic or radiation treatment; however, currently few studies have been reported that define the radiation-enhancingeffect of COX-2 inhibitors. We conducted in vitro radiation survival experiments using rat intestinal epithelial cells which were stably transfected with COX-2 cDNA in the sense (RIE-S) and antisense (RIE-AS) orientations toinvestigate the potential radiosensitizing effect of the selective COX-2 inhibitor, NS-398. Apoptosis was measured using 7-aminoactinomycin-D with flow cytometry to investigate underlying mechanisms for the effect of NS-398 on radiosensitivity. The same experiments were repeated with NCI-H460 humanlung cancer cells, which express COX-2 constitutively, and HCT-116 human colon cancer cells, which lack COX-2 expression. In vivo tumor growth delay assays were also performed with tumors formed by H460 and HCT-116 cells. Nodifference was observed in the intrinsic radiation sensitivity of RIE-S and RIE-AS cells exposed to radiation alone. However, 150-400 muM of NS-398 enhanced radiosensitivity in a concentration-dependent manner in RIE-S cellswith dose enhancement ratios of 1.2-1.9 at a surviving fraction of 0.25. However, this effect was not shown in RIE-AS cells. NS-398 enhanced radiosensitivity in H460 cells with a dose enhancement ratio of 1.8 but protected HCT-116 cells from the effects of radiation. Radiation-induced apoptosis wasenhanced by NS-398 in RIE-S and H460 cells but not in RIE-AS and HCT- 116 cells. Additionally, this radiation-enhancing effect in RIE-S cells seemed to be attributable to some mechanisms other than the reversal of radioresistance induced by COX-2. NS-398 (36 mg/kg) enhanced the effect of radiation on H460 tumors in vivo by an enhancement factor of 2.5, however, it did notenhance the radiosensitivity of HCT- 116 tumors (enhancement factor = 1.04). These in vitro and in vivo results suggest that selective COX-2 inhibitors enhance the effect of radiation on tumors that express COX-2 but not on COX-2-lacking tumors. This effect may be attributable to enhancement of radiation-induced apoptosis. Thus, selective COX-2 inhibitors may have potential as radiosensitizers for treatment of human cancers.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 13:32:58