钙调蛋白拮抗剂对人胃癌细胞效应机理的研究——钙调蛋白与磷酸二酯酶活性测定分析*

STUDIES ON THE MECHANISMS OF THE ACTION OF CALMODULIN ANTAGONIST——TRIFLUOPERAZINE ON CULTURED HUMAN STOMACH CARCINOMA CELLS: QUANTITATIVE ANALYSIS OF CALMODULIN AND PHOSPHODIESTERASE ACTIVITIES

我们曾经证明钙调蛋白(Calmodulin,CaM)拮抗剂三氟拉嗪(Trifluoperazine,TFP)有抑制人胃癌细胞增殖和诱导细胞形态向正常分化的效应。本文用CaM活性测定箱方法测定了TFP处理的人胃癌MGC-803细胞胞质内的CaM活性。同时也测定了磷酸二酯酶(Phosphodiesterase.PDE)活性的变化。结果表明TFP选择性抑制胞质内依赖Ca^(2+)/CaM的PDE活性。氨茶碱有抑制CaM活化PDE的作用。本文对TFP作用机理及在调控癌细胞增殖及分化中的意义进行讨论。

Motivated by our earlier demonstration that calmodulin (CaM) antagonist-trifluoperazine (TFP) effectively inhibits cell proli feration and DNA synthesis in human stomach car- cinoma MGC-803 cells with simultaneous induction of normalized cell morphology, this work was designed to investigate the mechanisms of TFP effect on MGC-803 cells By using biochemical assays, CaM and phosphodiesterase(PDE) activities in TFP treated MGC-803 cells were quantitatively analyzed with comparison to untreated control cells. TFP treated mouse ascitic hepatoma cells were analyzed as parallel. Results indicate that TFP selectively inhibits Ca^(2+)/CaM-dependent PDE activity rather than the PDE-binding activity of CaM in drug-treated cells of both types. However, both MGC-803 and mouse hepatoma cells exposed to aminophylline (2mmol/L) for 3 days or shorter time showed decrease in PDE-binding activity of CaM. The possible mechanisms concerning TFP effects and their role in regulating cell proliferation of MGC-803 cells were discussed