8－氯腺苷对小鼠肝癌H_（22）细胞的抑瘤作用研究

８－氯腺苷对小鼠肝癌Ｈ２２实体瘤的抑瘤率最高可达７１．７±１３．３％（ｉＰ）和６６．１±４．４６％（ｉｖ）（１００ｍｇ·ｋｇ－１ｄ－１×７ｄ）。腹水型Ｈ２２细胞经８－氯腺苷作用２４ｈ后，ｃＡＭＰ含量增加，ＤＡＧ含量下降；ＰＫＡＩ型调节亚基在药物作用后明显下降；凝胶阻滞分析表明，反式转录因子ＣＲＥＢ结合活性增加；原位杂交结果显示Ｐ５３抗癌基因表达增强。以上结果提示，８－氯腺苷抑瘤作用机制与第二信使系统和基因表达调控过程有关。

Effects of 8-chloroadenosine on murine hepatoma H_(22) cells

Chloroadenosine showed marked activity against murine hepatoma H22 solid tumor,at 100 mg·kg-1· d-1×7d. The inhibition rates of H22 were 71.3±13.3%(P<0.01)and 66.1±4.46%(P<0.01) by ip.and iv.administration respectively.8-Cl-Ado increased intercellular cAMP concentration but decreased disylglycerol amount in H22 ascites cells.Photoaffinity labeling/SDS-polyacrylamide gel electrophoresis assay indicated that 8-Cl-Ado greatly decreased R I(regulatory subunit of PKA)in the Cytosol of H22 Cells.Gel retardation analysis demonstrated the enhancement of CRE-binding activity after treatment for 24 hours with 8-Cl-Ado.Using in site hybridization,8-Cl-Ado induced antioncogene p53 expression.