摘要
BCR-ABL融合基因表达的肿瘤蛋白是慢性髓性白血病的主要致病因素.应用人BCR-ABL基因转染的细胞株FD-rv 210与其祖代细胞FDC-P1细胞组成的配对细胞株和不同的培养条件,建立了一个BCR-ABL酪氨酸激酶抑制剂的体外筛选体系,用于检测BCR-ABL酪氨酸激酶抑制剂的选择性.发现两种BCR-ABL酪氨酸激酶抑制剂AG 957和AG 490,对BCR-ABL阳性细胞和阴性细胞的增殖抑制作用相似;培养体系中有无祖代细胞增殖所需的细胞因子,对其增殖抑制作用无影响;AG 957短时作用于细胞即发生不可逆的增殖抑制现象.与已知的选择性BCR-ABL酪氨酸激酶抑制剂STI 571特性明显不同,提示这两种抑制剂作用呈非选择性.所建立的体外培养体系及不同的培养条件的组合,可用于筛选各种选择性的BCR-ABL酪氨酸激酶抑制剂.
The oncoprotein encoded by BCR-ABL fusion gene plays a pivotal role in the pathogenesis of chronic myeloid leukemia. A pair of cell lines, FDC-P1 and its derivative cell line transfected to overexpress BCR-ABL oncoprotein were used in various combinations of culture conditions to test the selectivity of two tyrosine kinase inhibitors AG 957 and AG 490. This in vitro selective system was verified by convincing results. The anti-proliferative effects of AG 957 and AG 490 on BCR-ABL positive or negative cell lines were similar and the existence of the growth factor needed for the proliferation of parental cell lines did not affect the anti-proliferative effect of the inhibitors. A short-term exposure of cells to AG 957 showed an irreversible inhibiting effect. As a recognized selective inhibitor of BCR-ABL tyrosine kinase, STI 571 demonstrated obviously different inhibitory effects on the counterpart of two cell lines. With different culture conditions, the established in vitro culture system could be useful to determine the specificity of the inhibitor to the target protein on BCR-ABL signal transduction pathway.
出处
《南京大学学报（自然科学版）》
CAS
CSCD
北大核心
2003年第5期554-558,共5页
Journal of Nanjing University（Natural Science）
