Effects of recombinant antisense c-myc adenovirus in induction of differentiation of HL-60 cells / 第三军医大学学报

ABSTRACT

Objectives To evaluate the potential of antisense c myc gene therapy for acute promyelocytic leukemia by investigating the biological effects and molecular mechanisms in induction of differentiation of HL 60 cell line using recombinant antisense c myc adenovirus (Ad AS c myc). Methods Cultured HL 60 cells treated with Ad AS c myc or Ad LacZ with polybrene and protamine sulfate were analyzed by X gal staining, morphology, MTT, flow cytometric analysis, RT PCR, and immunocytochemical techniques in vitro . Results HL 60 cells could be transfected effectively by Ad LacZ+protamine sulfate (79.8%). The level of c myc transcription and the version could be strongly inhibited by Ad AS c myc in the transfected HL 60 cells. Ad AS c myc could strongly inhibit the cell growth in HL 60 cells (51%). Ad AS c myc could reduce the ratio of nuclear/cytoplasm, and increase the activity of peroxidase in HL 60 cells. Ad AS c myc could lead to the blocking of G 0/G 1 phase in HL 60 cells. Ad AS c myc could also increase the expression of c fos in HL 60 cells. Conclusion The expression of Ad AS c myc can inhibit the growth and induce differentiation of HL 60 cells in vitro . The biological effects of Ad AS c myc may be closely associated with the activity of peroxidase and c fos gene in HL 60 cells. Ad AS c myc is of clinical potential in gene thera py for acute promyelocytic leukemia.