中文摘要：

目的研究羧胺三唑（CAI）对小鼠肺癌Lewis细胞（LLC）中环腺苷酸（cAMP）相关磷酸二酯酶（PDE）活性的影响；研究腺苷酸环化酶激动剂Forskolin是否能增强CAI的抑瘤作用。方法通过改良的Thompson和Appleman两步同位素法对LLC细胞中cAMP相关PDE的活性进行检测，以PDFA特异性抑制剂洛利普兰（RoD作为CAI的阳性对照；通过台盼蓝斥染实验对LLC活细胞进行计数，检测Forskolin对CAI抑瘤作用的影响，以双丁酰环腺苷酸（db-cAMP）验证LLC细胞对cAMP含量增加的敏感性。结果CAI可剂量依赖性地抑制LLC细胞中cAMP相关PDE的活性，CA／与Rol的IC50分别为5．62×10击moFL和1．88×10^-8moFL。Forskolin和db-cAMP均可剂量依赖性地抑制LLC细胞的活性。CAI与Forskolin合用的抑瘤作用显著优于CAI单用，CAI5μmol／L单用时的抑制率为（32．9±10．3）％，与Forskolin10lamol／L合用后抑制率可达（67．4±3．76）％（P〈0．05）。结论抑制cAMP相关PDE的活性可能是CA／抑制LLC细胞活力的机制之一。通过与升高CAMP的药物如Forskolin合用，可进一步优化CAI的抗肿瘤作用。

英文摘要：

Objective To investigate the effect of carboxyamidotriazole （CAI） on adenosine 3＇, 5＇-cyclic monophosphate specific phosphodiesterase （cAMP-PDE） in Lewis lung carcinoma （LLC） ceils. To investigate whether adenylate cyclase （AC） activator Forskolin can enhance the anti-cancer effect of CAI. Methods PDE activity was determined with the modification of two-step method of Thompson and Appleman. PDE4 specific inhibitor Rolipram （Rol） was applied as the positive control. The live LLC cells were counted with Trypan blue excluding test. Dibutyryl-cAMP was applied to test the sensitivity of LLC cells to cAMP treatment. Results CAI could inhibit cAMP-PDE activity in LLC cells dose-dependently. The ICs0 of CAI and Rol were 5.62×10^-6 mol/L and 1.88×10-8 tool/L, respectively. Both Forskolin and db-cAMP could inhibit LLC ceil growth dose-dependently. The inhibition ratio of CAI and Forskolin combination was significantly higher than CAI alone. The inhibition ratio of 5 pmol/L CAI and 10/amoFL Forskolin was （32.9±10.3）% and （67.4±3.76）% （P〈0.05）, respectively. Conclusion Inhibition of cAMP-PDE may be one of the anti-cancer mechanisms of CAI. Its anti-cancer effect can be enhanced by combining with cAMP elevating drugs such as Forskolin.