The COX-2 inhibitor NS398 selectively sensitizes hypoxic HeLa cells to ionising radiation by mechanisms both dependent and independent of COX-2

Publication date: Available online 28 January 2020Source: Prostaglandins & Other Lipid MediatorsAuthor(s): Shailendra Anoopkumar-Dukie, Tom Conere, Aileen Houston, Liam King, David Christie, Catherine McDermott, Ashley AllshireAbstractIt is widely accepted that the hypoxic nature of solid tumors contribute to their resistance to radiation therapy. There is increasing evidence that cyclooxygenase-2 (COX-2) contributes to increased resistance of tumors to radiation therapy. Several studies demonstrate that combination of COX-2 selective inhibitors with radiation therapy selectively enhances radioresponsiveness of tumor cells. However, the majority of these studies utilised suprapharmacological concentrations under normoxic conditions only. Furthermore, the mechanism by which these agents act remain largely unclear. Therefore, the aim of this study was to determine the impact of COX-2 selective inhibitors on both normoxic and hypoxic radiosensitivity in vitro and the mechanisms underlying this. Because of the close, reciprocal relationship between COX-2 and p53 we investigated their contribution to radioresistance. To achieve this we exposed HeLa, MCF-7 and MeWo cells to the COX-2 selective inhibitor, NS398 (10µM). NS398 (10µM) selectively sensitized hypoxic HeLa and MCF-7 but not MeWo cells to ionising radiation (5 Gy). Furthermore, while knockdown of COX-2 with siRNA did not affect either normoxic radiosensitivity in HeLa cells, the radiosensitisation observed with NS398 w...
Source: Prostaglandins and Other Lipid Mediators - Category: Lipidology Source Type: research