紫草萘醌(阿卡宁)衍生物SYUNZ-4的抗瘤作用研究

 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。

Antitumor Effect of Alkannin Derivative,SYUNZ-4

OBJECTIVE To explore in vitro cytotoxicity and in vivo antitumor effect of semi-dynthesized alkannin derivatives of3,11-bis(2-hydroxyethanesulfonyl)-6-isohexenylnaph-thazarin,SYUNZ-4].METHODS The cytotoxicity of SYUNZ-4 was assayed using MTT method.Efficiency was evaluated using IC₅₀.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 IC₅₀ were 0.30～7.75 mg·L^-1.The IC50 of SYUNZ-4 to 2 kinds of MDR cells (MCF-7/ADR and KBV200) were 1.96 and 7.78 mg·L^-1.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×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.