Effects of recombinant epidermal growth factor receptor antisense adenovirus combined with irradiation on breast cnacer cells / 中华放射肿瘤学杂志

ABSTRACT

Objective To investigate the effects of a recombinant antisense adeno virus for epidermal growth factor receptor (EGFR) combined with irradiation on b reast cancer cells.Methods Human EGFR cDNA fragment was subcloned in the oppos ite orientation to the cytomegaloviral promoter and inserted into a E1/E3-delet e d type 5 adenoviral vector to obtain AdE5 construct which expresses EGFR antisen se RNA. Combined with ?-ray irradiation, its effects on clonogenicity and cell cycle phase distribution were studied in a human breast cancer line MDA-MB-231 . Results EGFR protein expression was dramatically inhibited in MDA-MB-231 cell s after AdE5 infection. The post-irradiation clonogenicity was reduced by AdE5 in a viral and irradiation dose-dependent manner. Further cytometric analysis show e d that AdE5 infection at a?MOI of 300?pfu/cell induced a cell cycle progre ssion from radio-resistant G 0+G 1 phases to radiosensitive G 2+M phases, resultin g in a synergistic effect after combination of these two treatments. Conclusions The t ransduction of EGFR antisense RNA by adenoviral vector is effective for antisens e strategy targeting EGFR, and increases the cell-killing effect of ionizing radiation on breast cancer cells.