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Radiation Sensitivity of Human Carcinoma Cells Transfected with Small Interfering RNA Targeted against Cyclooxygenase-2

Author's Affiliation: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Sanjeewani T. Palayoor, Radiation Oncology Branch, National Cancer Institute, NIH, Room B3B69, Building 10, 9000 Rockville Pike, Bethesda, MD 20892-1002. Phone: 301-435-7502; Fax: 301-496-7871; E-mail: Palayoor{at}mail.nih.gov.

Purpose: Cyclooxygenase-2 (COX-2) is considered a potential target for cancer therapy, because COX-2 levels are elevated in the majority of human tumors compared with the normal tissues. COX-2 inhibitors inhibit tumor growth and enhance radiation response in vitro as well as in vivo. However, the precise role of COX-2 in radiation response is not clear. The purpose of the present study was to investigate the in vitro radiosensitivity of tumor cells as a function of COX-2 expression.

Experimental Design and Results: PC3 and HeLa cells express COX-2 protein constitutively. We silenced the COX-2 gene in these cells using small interfering RNA (siRNA). Transfection of PC3 cells with 100 nmol/L siRNA targeted against COX-2 resulted in reduction of COX-2 protein by 75% and inhibition of arachidonic acid–induced prostaglandin E₂ synthesis by 50% compared with the vehicle control. In HeLa cells, 100 nmol/L COX-2 siRNA inhibited COX-2 protein expression by 80%. Cell cycle analysis showed that transfection with COX-2 siRNA did not alter the cell cycle distribution. Radiosensitivity was determined by clonogenic cell survival assay. There was no significant difference in the radiosensitivity of cells in which COX-2 was silenced compared with the cells transfected vehicle or with negative control siRNAs (enhancement ratio = 1.1).

Conclusions: These data indicate that the in vitro radiosensitivity of tumor cells is minimally dependent on the cellular COX-2 status. Given that a number of potential mechanisms are attributed to COX-2 inhibitors for radiosensitization, specific intervention of COX-2 by RNA interference could help elucidate the precise role of COX-2 in cancer therapy and to optimize strategies for COX-2 inhibition.

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