SIOC-AA-005的抗肿瘤作用机制研究

探讨SIOC-AA-005抗肿瘤的作用机制.采用测定HT-29 细胞线粒体膜流动性、线粒体ATP含量、线粒体ATP酶活性及NADH-CoQ氧化还原酶活性、细胞质膜NADH氧化酶活性的方法,对其作用机制进行了深入探讨;SIOC-AA-005在10 nmol/L剂量下可明显降低线粒体膜的流动性,并使线粒体膜电位显著升高;在此浓度下,SIOC-AA-005还可使HT-29细胞内的ATP耗竭,ATP酶活性受到抑制,线粒体中能量产生过程受阻.在胞外反应体系中,SIOC-AA-005对NADH-CoQ氧化还原酶有强烈的抑制作用,对细胞质膜NADH氧化酶也具有较强的抑制作用.SIOC-AA-005可能是通过抑制线粒体NADH-CoQ氧化还原酶、抑制细胞质膜NADH氧化酶以及线粒体ATP酶活性,从而使线粒体膜流动性下降,膜电位升高,细胞内ATP耗竭,最终使肿瘤细胞死亡。

Study on mechanism of SIOC-AA-005 on antitumor activity

To research the mechanism of SIOC - AA - 005 antitumor activity. This paper carries out by fluidity of mitochondria membrane, mitochondria membrane potential, ATP concentration in cells, ATPase activity of mitochondria, NADH - CoQ oxyreductase activity of mitochondria, NADH Oxydase activity of membrane. The results indicated that the fluidity mitochondria membrane in HT - 29 cells was decreased significantly when treated with 10 nmol/L SIOC - AA - 005 and the mitochondria membrane potential was increased markedly. Under this concentration, the ATP concentration was decreased and ATPase had been inhibited. SIOC-AA - 005 could inhibit NADH - CoQ oxyreductase activity on mitochondria and the membrane NADH oxydase activity in HT - 29 cells in vitro. The mechanism underlying inhibition effects shows that SIOC - AA - 005 inhibit mitochondria NADH - CoQ oxyreductase and membrane NADH oxydase and mitochondria ATPase. The inhibition on these enzymes makes the fluidity of mitochondria membrane decrease, membrane potential increase, and ATP in the cells deplete, then the tumor cells die of energy starvation.