[Effect of shRNAmir lentiviral vector-mediated COX-2 silencing on the radiosensitivity of nasopharyngeal carcinoma cells].

ABSTRACT

OBJECTIVE: To evaluate the effect of COX-2 silencing on the radiosensitivity of a nasopharyngeal carcinoma (NPC) cell line C666-1. METHODS: Anti-COX-2 C666-1 cell line with COX-2 gene silencing mediated by shRNAmir lentiviral vector and the control cell line Anti-GL-2 C666-1 were exposed to various radiation doses. The clonogenic survival assay and curve fitting was used to calculate the radiobiological parameters and the sensitization enhancement ratio after the radiation. Cell cycle changes were assessed after the exposure by flow cytometric analysis. In a BALB/c nude mouse model, the growth curve of the xenografts was generated and the tumor growth inhibition rate was calculated. RESULTS: Compared with the control cells, Anti-COX-2 C666-1 cells showed obviously lowered values of SF2, D0 and Dq but significantly increased α/ß with a sensitivity enhancement ratio of 1.4014. COX-2 gene silencing increased the inhibition rate of the tumor xenografts after the radiation, and caused also decreased percentage of G2/M arrest resulting from the exposure. CONCLUSION: Stable COX-2 silencing in NPC cells can improve the effect of radiotherapy both in vitro and in vivo. By changing the radiobiological parameters, genetically based COX-2 inhibitor may be a potentially promising radiosensitizer of NPC.