钙调素拮抗剂-O-丹磺酰基小檗胺对磷酸二酯酶及肺细胞增殖的影响

EFFECT OF CaM ANTIGNOIST-O-DANSYLBERBAMINE (DB) ON PDE AND PROLIFERATION OF LUNG CELLS IN VITRO

测定了自行合成的含疏水性荧光基团的小檗胺衍生物 (O-丹磺酰基小檗胺 ,DB)对依赖于钙调素 (Ca M)的磷酸二酯酶 (PDE)活性的影响 ;比较了 DB对体外培养的正常细胞 (人胚肺细胞 HEL)和恶性肿瘤细胞 (肺巨细胞癌 PG)增殖的影响和 DB处理后肿瘤细胞中原癌基因和抑癌基因表达水平的变化 .结果表明 ,DB对依赖于Ca M的 PDE有明显的抑制作用 ,其 IC50 值为 3 μmol/L.DB对体外培养的 PG细胞的增殖有明显的抑制作用 ,抑瘤的 IC50 值小于 1μmol/L ;而此浓度的 DB对 HEL细胞的增殖影响很小 (1μmol/L的浓度 ,存活率仍维持在91 % ) ,说明一定浓度的 DB具有选择性杀伤肿瘤细胞的能力 .此外 ,DB对 PG细胞中的原癌基因和突变的抑癌基因的表达均有一定的影响 .

DB was synthesized with chemical method and contained fluorophore. This paper studied the effect of DB on CaM dependent PDE activity and compared their action on tumor cells (human lung cancer cells, PG) and normal embryo lung cells (HEL) proliferation in vitro . The effect of expression of oncogenes (c myc, c H ras) and tumor suppressor genes (p53,Rb) in PG cells. After treated with DB, experimental results showed that the first, DB can inhibit CaM dependent PDE activity, the IC 50 value is 5μmol/L; the second, DB strongly inhibits PG cell proliferation and does less harm to normal cells; the third, DB also inhibits the expression of c myc and c H ras genes at the translation level and reverses the malignant lung cancer cell proliferation due to high mutation frequency of p53 and Rb genes.