Effects of retinoic acid on the radiosensitization in HL-60 cells transfected with IFN? expression vector containing retinoic acid response element / 第三军医大学学报

ABSTRACT

Objective To study the effects of retinoic acid on the radiation sensitivity in HL-60 cells transfected with the IFN? expression vector containing retinoic acid response element and its possible mechanism.Methods HL-60 cells were transfected with pRARE4-IFN?,then treated by all-trans retinoic acid at the dose of 2?10~(-7)mol/L and/or irradiation under 4 Gy.The cellular proliferation capacity was observed with MTT assay,the cell apoptosis was measured with DNA fragmentation rate,the protein expression of caspase-3 was analyzed with Western blotting.Meanwhile,the activity of caspase-3 was examined.Results After HL-60 and HL-60~(IFN?)cells were treated by RA and/or radiation,the cellular proliferation capacity was decreased,the DNA fragmentation rate was increased,the protein expression and activity of caspase-3 were up-regulated.These changes were more apparent in transfected cells than non-transfected cells,and more significant in cells treated by radiation and RA than that treated by radiation or RA alone.The special caspase-3 inhibitor,DEVD-CHO could inhibit the activity of caspase-3 and impair the growth inhibition and apoptosis induced by RA and/or radiation.Conclusion Our study demonstrated that DNA fragmentation and growth inhibition of transfected and non-transfected cells induced by radiation could be enhanced with RA.The up-regulated expression and activity of caspase-3 may play a partial role in cell apoptosis induced by RA and radiation.