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喜树碱(camptothecin,CPT)是从植物喜树中分离得到的一种生物碱,由于其毒性作用大,抗肿瘤作用相对较弱而未在临床广泛使用.近年来,由于合成了一系列具有比喜树碱更强抗癌活性的衍生物,以及对其作用更深入的研究,对喜树碱类药物重新受到重视.特别是从喜树中分离得到的羟基喜树碱(hydroxycamptothecin,HCPT),无论从基础实验研究,还是临床应用,均证明该药是一种有效的抗癌药物.本文就羟基喜树碱类药物在治疗进展期大肠癌方面的最新进展作一综述.一、羟基喜树碱的作用机制羟基喜树碱为S期特异性的抗肿瘤药物,拓扑异构酶I(Topo-I)为CPT的主要作用部位,由于CPT稳定了Topo-I-DNA的断裂复合物,抑制复制的进行,从而阻遏了复制叉的移动,同时CPT使Topo-I-DNA断裂复合物的物理特性发生改变,当去掉药物后,也不能使断裂复合物复原,形成了CPT的S期特异性细胞杀伤作用的机制.因为细胞中Topo-I的表达水平与对药物的敏感性呈正相关,故Topo-I高表达的细胞株对CPT高度敏感,而无Topo-I活力的细胞株则对CPT耐药.在结肠癌患者手术切除的肿瘤标本组织中,Topo-I酶含量大约是正常组织的14～16倍,提示CPT类药物对结肠癌有较高的疗效.同时细胞内cAMP和cGMP比率的变化在一定程度上控制着细胞的生长与分化,而羟基喜树碱能改变cAMP?
Camptothecin (CPT) is an alkaloid isolated from the plant Camptotheca acuminata. Because of its toxic effect and relatively weak antitumor effect, it is not widely used in clinic. In recent years, due to the synthesis of a series of Derivatives with stronger antitumor activity than camptothecin, and more in-depth studies on their effects, have renewed attention for camptothecins, especially hydroxycamptothecin (HCPT) isolated from Camptotheca acuminata. Both the basic experimental study and the clinical application have proved that the drug is an effective anti-cancer drug. This article reviews the latest advances in the treatment of advanced colorectal cancer with hydroxycamptothecins. The mechanism of action of the tree base is hydroxycamptothecin as an S phase-specific anti-tumor drug. Topo-I (Topo-I) is the main site of action of CPT, as CPT stabilizes Topo-I-DNA fragmentation complexes. Inhibiting the progress of replication, thus suppressing the movement of the replication fork, the CPT causes the physical properties of the Topo-I-DNA fragmentation complex to change. When the drug is removed, the fragmented complex cannot be reconstituted to form the S-phase specificity of CPT. The mechanism of sexual cell killing. As the expression level of Topo-I in cells is positively correlated with the sensitivity to drugs, Topo-I highly expressing cell lines are highly sensitive to CPT, while non-Topo-I viable cell lines are resistant to CPT. The content of Topo-I enzyme is approximately 14-16 times higher than that of normal tissue in patients with surgically resected tumor specimens, suggesting that CPT drugs have a higher curative effect on colon cancer. Meanwhile, the ratio of intracellular cAMP and cGMP changes to a certain extent. Control cell growth and differentiation, and hydroxycamptothecin can change cAMP?