斑蝥素衍生物与铂络合物抗癌活性的实验研究

Experimental Study on Anti Cancer Effect of Cantharidine Derivatives and Platinum Complex

目的：研究４种斑蝥素衍生物与铂络合物（斑铂，Ｄｐｔ）对实验动物的抗癌作用，力图开发一种新型的铂族金属抗癌药。方法：以Ｓ１８０肉瘤、Ｈ２２肝癌实体瘤及其腹水瘤小鼠为实验动物，通过腹腔或静脉给予不同剂量的４种化合物Ｄｐｔ１－１５、Ｄｐｔ５－１０、Ｄｐｔ１２－３、Ｄｐｔ６－２，分别观察药物对小鼠瘤重及存活天数的影响，以顺铂为阳性对照，生理盐水为阴性对照。所有数据进行ｔ检验。结果：４种斑铂（Ｄｐｔ１－１５、Ｄｐｔ５－１０、Ｄｐｔ１２－３、Ｄｐｔ６－２）均有抗癌活性。其中Ｄｐｔ５－１０、Ｄｐｔ１－１５对小鼠Ｓ１８０肉瘤及Ｈ２２实体瘤的抑制率与顺铂相似；Ｄｐｔ５－１０对Ｈ２２腹水瘤小鼠生命延长率与顺铂相似；Ｄｐｔ１－１５的有效剂量毒性较大。结论：斑铂是有效的新型抗癌化合物，其中Ｄｐｔ５－１０抗癌作用较好，应进一步改进药物溶解性，并从与顺铂抗药性不同方面开发利用。

Objective: To certify the anti tumor effects of the four Cantharidine derivatives and platinum complex on transplanted tumor in mice to search for new anti tumor drugs. Methods: Complex of four Cantharidine derivatives (Dpt 1-15, Dpt 5-10, Dpt 12-3 and Dpt6-2) and platinum were given to tumor beating mice of transplanted S 180 sarcoma, H 22 solid hepatocarcinoma and ascites hepatocarcinoma through intraperitoneal or intravenous injection, and the effect of treatment on tumor weight and survival of animal were observed. Cisplatin was used as positive control and 0.9% normal saline used as negative control. All data were treated with t test. Results: All the four complex had anti tumor effect. The inhibition rate of Dpt5-10 and Dpt1-15 on S 180 sarcoma and H 22 solid hepatocarcinoma and the survival prolongation rate of Dpt5-10 on H 22 ascites hepatocarcinoma were similar to those of cisplatin. The toxicity of effective dose of Dpt1-15 was rather high. Conclusions: Cantharidine derivatives and platinum complex is new effective anti tumor drug, among them the Dpt5-10 is the most effective one. Further study for improving the solubility of drug is necessary and study the difference of cross resistance between the new complex and cisplatinum.