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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 investigate the cytotoxicity of semi-synthesized Akanin derivative-3,11-bis(2-hydroxyethyl thiol)-6-isonaphthoquinone (codenamed SYUNZ-4) in vitro on various human cancer cells. Role and anti-tumor effect in vivo. Methods Cytotoxicity in vitro was measured using the tetrazolium blue (MTT) method and evaluated by the half inhibitory concentration (IC50). The anti-tumor effect in vivo is the use of a mouse xenograft model and a human cancer cell nude mouse xenograft model. Results In vitro cytotoxicity assay showed that SYUNZ-4 had strong cytotoxicity on 7 kinds of human cancer cells, their IC50 was 0.32-7.75 mg·L-1, IC50 of resistant cell lines MCF-7/Adr and KBV200. They were 1.96 and 7.87 mg·L-1, respectively. In vivo anti-tumor tests, SYUNZ-4 at 2.0, 6.0 and 10.0mg · kg-1, ip, q2d × 10d, the inhibition rate of mouse sarcoma S-180 and mouse liver cancer HepS were 31.5% ~ 69.7% and 45.9%~67.5% (P<0.05~0.01). The inhibitory rates of SYUNZ-4 at 2.0, 6.0, 10.0, and 14.0 mg·kg-1 were 30.2%-58.1% (P<0.05-0.01) in mice with Ehrlich ascites carcinoma. Under the conditions of 6.0 and 10.0 mg·kg-1,ip,q3d×18d, the inhibitory rate of SYUNZ-4 on human lung adenocarcinoma (GLC-82) transplanted tumor in nude mice was 48.4% and 61.7% (P<0.001). The tumor inhibition rates of human nasopharyngeal carcinoma cells (CNE2) in nude mice at doses of 2,6 and 10 mg.kg-1 were 35.5%, 41.9% and 48.3%, respectively, P<0.01-0.001. Conclusion The newly synthesized SYUNZ-4 derivative has strong cytotoxicity and anti-tumor activity in mice.