IFN－γ联合rhTNF－α抑制白血病细胞c－myc原癌基因的表达

INHIBITION OF PROTO-ONCOGEAE c-myc EXPRESSION WITH RECOMBINANT HUMAN TUMOR NECROSIS FACTOR-αAND INTERFERORN-rIN HL-60 CELL LINES AND ACUTE MYLLOCYTIC LEUKEMIC FRESH CELLS

将干扰素（ＩＦＮ－ｒ）和肿瘤坏死因子（ＴＮＦ－α）与人白血病细胞株及急性髓细胞白血病（ＡＭＬ）病人原代白血病细胞体外液相共育，用细胞，总ＲＮＡ样品与￣（３２）Ｐ标记的ｃ－ｍｙｃＤＮＡ探针打点杂交，我们观察了ＩＦＮ－ｒ联合ＴＮＦ－α作用ＨＬ－６０细胞，ＴＮＦ作用病人原代白血病细胞对其ｃ－ｍｙｃ癌基因表达的影响。结果发现：１００Ｕ／ｍｌ和５００Ｕ／ｍｌ的ＩＦＮ－ｒ可明显促进５０Ｕ／ｍｌＴＮＦ－α对ＨＬ－６０细胞ｃ－ｍｙｃ表达的抑制作用；８例ｃ－ｍｙｃ高表达的ＡＭＬ病人，经５０Ｕ／ｍｌＴＮＦ作用后，其ｃ－ｍｙｃｍＲＮＡ水平发生显著性减低。结果证明了ＩＦＮ－ｒ具有协同ＴＮＦ－α抑制ＨＬ－６０白血病细胞ｃ－ｍｙｃ癌基因表达的作用，ＴＮＦ－α对白血病细胞株及病人原代白血病细胞ｃ－ｍｙｃｍＲＮＡ水平均有明显的抑制效应。

L-60 cell lines and AM L fresh bone marrow cells were incubated with rhTNF-α and rhIFN-r in suspension culture system. Then total RNA was prepared for dot blot with￣(32)P nick-translated c-myc DNA probe. The expression changes of c-myc oncogene when the HL-60 cell lines were treated with rhTNF-αand IFN-rand the AML fresh bone marrow cells treated with rhTNF-α alone were ob- served.The results showed that when the HL-60 cells were treated with 100U / ml or 500U/ml IFN-r and 50U / ml rhTNF-αfor 8 hours,the expression of c-myc oncogene can be inhibited remarkably. The combination of rhIFN-rand rhTNF-αshows synergistic effect on inhibition of c-myc expression. High expression of c-myc was found in 8 patients with AML;c-myc mRNA level decreased remarka- bly after treatment of fresh bone marrow cells with 50U / ml rhTNF-α for 12 hours in 6 cases,while the remaining 2 cases showed miminal changes.The results demonstrate that rhTNF-αhave inhibitive ef- fect on c-myc expression in HL-60 cells and AML fresh leukemic cells.It also indictes the possibility of treating AML with low-dose rhTNF-α.