Effect of F951,a novel bcl-2 antisense oligodeoxynucleotide,on human leukemia transplanted subcutaneously in nude mice / 中国药理学通报

ABSTRACT

Aim To study the inhibitory effects of F951,a novel bcl-2 antisense oligodeoxynucleotide,on expression of bcl-2,growth of tumor and survival time of nude mice transplanted subcutaneously with acute myeloid leukemia.Methods HL-60 cells with high expression of bcl-2 were proliferated in vitro.The models of the nude mice with HL-60 cells were established by subcutaneous transplantation with drugs directly injected.The effects of F951 and F951 with low dose Ara-c on growth of tumor and survival time of mice with tumor were observed.The expressions of bcl-2 mRNA in the tumors implanted were detected by fluorescent quantitation RT-PCR.The morphologic structure of tumor tissues was assayed by light microscope.Results After each group mice with tumors were treated for 14 days,the volume,the weight of tumor and the bcl-2 mRNA expression of tumor tissue were shown respectively as follows NS control group(15.17?3.40)cm3、(12.69?0.92)g、9.79?104 Copies??g-1;FNS group(15.91?3.77)cm3,(12.38?1.21)g;8.31?104 Copies??g-1;Ara-C group(1.24?0.55)cm3,(2.32?0.49)g,2.59?104 Copies??g-1;F951 group(2.6?1.55)cm3,(3.53?0.67)g;1.01?103 Copies??g-1;F951+Ara-C group(0.62?0.48)cm3,(1.05?0.63)g,9.5?102 Copies??g-1.The data above showed that F951 could downregulate the expression of bcl-2 in nude mice with HL-60 cells xenograft and inhibit growth of tumor.The growth of tumor of F951 group was reduced,and the inhibitory rate was 72.18%,there was significant difference comparing control groups with NS and FNS(P