三肽氮芥类化合物MF13联合化疗的抗肝癌作用  

Combination chemotherapy of L-proline-m-bis(2-chloroethyl) amino-L-phenylalanyl-L-norvaline ethyl ester hydrochloride with anti-cancer drugs in human hepatocellular carcinoma

作　　者：胡琼莹[1,2] 蒋建东[3,2] 宋丹青[2] 梁勇[1] 韩燕星[3] 

机构地区：[1]台州学院医学院,浙江台州318000 [2]中国医学科学院北京协和医学院医药生物技术研究所,北京100050 [3]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2017年第6期911-920,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(398708889);浙江省公益技术应用研究项目(2016F81G2170011)

摘　　要：L-脯氨酸-间-双(2-氯乙基)胺基-L-苯丙氨酰基-L-正缬氨酸乙酯盐酸盐(MF13)是一个新颖的含三肽的氮芥类化合物。本课题组以往的体内外研究数据表明,MF13单药给药时,对多种不同来源的人肝癌细胞系均有较强的抗增殖活性。本文主要研究MF13与其他抗肿瘤药物联合使用时对肝癌的抑制作用。联合化疗体外实验结果显示,MF13与丝裂霉素C(MMC)在适宜浓度下联合应用时,对Bel-7402细胞的抗增殖活性有协同作用;MF13与长春新碱(VCR)联用无协同作用。联合化疗裸鼠体内实验结果表明,2 mg·kg^(-1) MF13与50 mg·kg^(-1)环磷酰胺(CTX)或2 mg·kg^(-1) MMC联用,协同作用显著;然而,2 mg·kg^(-1) MF13与0.3 mg·kg^(-1) VCR联合使用时无协同作用。联合化疗的体内外实验结果一致。本研究结果表明,无论单药给药还是联合化疗,MF13都是一个有潜在应用前景的抗肝癌化合物。L-Proline-m-bis （2-chloroethyl） amino-L-phenylalanyl-L-norvaline ethyl ester hydro chloride （MF13） is a new anticancer tripeptide. Our previous study in vitro and in vivo showed that MF13 had anti-proliferative activities in a panel of human hepatocellular carcinoma （HCC） cell lines from different origin. In the present study, we focused on the inhibition effect on HCC of MF13 combined with other anti-cancer drugs. The results of combination chemotherapy in vitro indicated that the combination of MFI3 with mitomycin C （MMC） at appropriate concentrations led to a synergistic effect; however, the combination of MF13 with vincristine （VCR） showed no synergistic effect. In the Bel-7402 tumor bearing nude mice, the antitumor effect of the groups of 2 mg.kg-1 MFI3 ＋ 2 mg.kg-1 MMC or 2 mg-kg-1 MFI3 ＋ 50 mg.kg-1 cyclophosphamide （CTX） exhibited synergistic anticancer efficacies while the group of 2 mg.kg-1 MF13 ＋ 0.3 mg.kg-1 VCR did not have the same effect. Based on our data, we believe that MF13 can be considered as a potential agent against human hepatocellular carcinoma no matter how treated, alone or combined with other drugs.

关 键 词：肝癌 盐酸氮芥 联合化疗 协同作用 

分 类 号：R962[医药卫生—药理学]