紫草萘醌(阿卡宁)衍生物SYUNZ-4的抗瘤作用研究

Antitumor Effect of Alkannin Derivative,SYUNZ-4

目的探讨半合成的一种新的阿卡宁衍生物-3,11-双（2-羟乙巯基）-6-异己萘茜（代号为SYUNZ-4）体外对各种人癌细胞的细胞毒作用和体内的抗瘤作用。方法体外细胞毒作用是应用四氮唑蓝（MTT）法测定,以半数抑制浓度（IC50）进行评价。体内抗瘤作用是应用小鼠移植瘤模型和人癌细胞裸鼠移植瘤模型。结果体外细胞毒试验表明,SYUNZ-4对7种人癌细胞有强的细胞毒作用,它们的IC50为0.32-7.75mg·L^-1,对耐药细胞株MCF-7/Adr和KBV200的IC50分别为1.96和7.87mg·L^-1。体内抗瘤试验,SYUNZ-4在2.0,6.0和10.0mg·kg^-1,ip,q2d×10d,对小鼠肉瘤S-180和小鼠肝癌HepS的抑瘤率分别为31.5%-69.7%和45.9%-67.5%（P〈0.05-0.01）。SYUNZ-4在2.0,6.0,10.0和14.0mg·kg^-1,对小鼠肿瘤艾氏腹水癌实体型ESC的抑瘤率为30.2%-58.1%（P〈0.05-0.01）。在6.0和10.0mg·kg^-1,ip,q3d×18d条件下,SYUNZ-4对人肺腺癌（GLC-82）裸鼠移植瘤的抑瘤率为48.4%和61.7%（P〈0.001）;在2,6和10mg.kg^-1剂量下对人鼻咽癌细胞（CNE2）裸鼠移植瘤的抑瘤率分别为35.5%、41.9%和48.3%,P〈0.01-0.001。结论新合成的紫草醌衍生物SYUNZ-4具有强的细胞毒作用和抗小鼠肿瘤作用。

OBJECTIVE To explore in vitro cytotoxicity and in vivo antitumor effect of semi-dynthesized alkannin derivatives of [ 3,11-bis （2-hydroxyethanesulfonyl） -6-isohexenylnaph-thazarin, SYUNZ-4 ]. METHODS The cytotoxicity of SYUNZ-4 was assayed using MTF method. Efficiency was evaluated using ICs0. In vivo antitumor effect was tested by models of transplanted tumor in mice and nude mice. RESULTS SYUNZ-4 presented strong cytotoxicities on 7 kinds of human cancer cell lines. The ICs0 were 0. 30 - 7.75 mg · L^-1. The IC50 of SYUNZ-4 to 2 kinds of MDR cells （MCF-7/ADR and KBV2o0） were 1.96 and 7.78 mg ~ L-I. Under the doses of 2.0, 6. 0 and 10. 0 mg · kg^- 1, ip, q2d × 10 d, the tumor inhibitory rates of SYUNZ-4 to against sarcoma S-180 and HepS in mice, were 31.5% - 69. 7% and 45.9% - 67.5%, respectively （P 〈 0. 01 - 0. 001 ）. Under the doses of 2. 0, 6. 0, 10. 0 and 14.0 mg · kg^-1, the tumor inhibitory rates on tumor ESC in mice were 30. 2% -58. 1% （P 〈 0. 05 -0. 01 ）. Under the doses of 6. 0 and 10. 0 mg · kg^-1, ip, q3d x 18 d, the tumor inhibitory rates of SYUNZ-4 to human lung adenocarcinoma cell （GLC-82） xenografts in nude mice were 48.4% and 61.7% （P 〈0. 01 -0. 001 ）. Under the doses of 2.0, 6.0 and 10. 0 mg · kg^-1 , the tumor inhibitory rates of SYUNZ-4 on human nasopharyngeal carcinoma （ CNE2 ） xenografts in nude mice were 35.5% , 41.9% and 48.3%, respectively （ P 〈 0. 01 - 0. 001 ）. CONCLUSION SYUNZ-4 has strong cytotoxity and antitumor activity.