Chiba Y, Kubota T, Watanabe M, Otani Y, Teramoto T, Matsumoto Y, Koya K, Kitajima M
Department of Surgery, School of Medicine, Keio University, Tokyo, Japan.
J Surg Oncol. 1998 Oct;69(2):105-10. doi: 10.1002/(sici)1096-9098(199810)69:2<105::aid-jso11>3.0.co;2-0.
1-Ethyl-2-¿[3-ethyl-5-(3-methylbenzothiazolin-2-yliden)]-4-+ ++oxothiazolidin-2-ylidenemethyl¿pyridium chloride (MKT-077, formerly known as FJ776), a delocalized lipophilic cation, is known to accumulate in the mitochondria, according to the negative potential inside the mitochondria, and exert its cytotoxicity.
The single-cell suspensions of human cancer cell lines, human spleen cells, and fresh cancer specimens obtained from patients with gastric carcinoma were used for the 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) assay.
The antitumor activity of MKT-077 was dose and concentration related, and 50% inhibitory concentrations (IC50) ranged from 1.7 to 14.3 microg/ml, with a mean +/- standard deviation (SD) of 8.4 +/- 4.6 microg/ml. The IC50 of fresh surgical spleen-cell specimens ranged from 0.34 microg/ml to >100 microg/ml in a 48 h incubation, with a mean +/- SD of 66.5 +/- 37.7 microg/ml. When the antitumor activity of MKT-077 was compared between gastric cancer cells and spleen cells obtained from the same patient, the concentration-dependent antitumor activity of this agent was obvious in the cancer cells, while no significant cytotoxicity was observed in the spleen cells. The fresh surgical specimens of gastric cancer showed higher sensitivity to MKT-077 than did spleen cells at a concentration of 30 microg/ml, with a statistically significant difference at P < 0.05.
The selective antitumor activity of MKT-077 was confirmed using fresh surgical specimens and warrants further investigation.
1-乙基-2-[[3-乙基-5-(3-甲基苯并噻唑啉-2-亚基)]-4-氧代噻唑烷-2-亚甲基]吡啶氯化物（MKT-077，原称FJ776）是一种离域亲脂性阳离子，已知其会根据线粒体内的负电位在线粒体中蓄积并发挥细胞毒性作用。
人癌细胞系、人脾细胞的单细胞悬液以及取自胃癌患者的新鲜癌组织标本用于3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H四唑溴盐（MTT）检测。
MKT-077的抗肿瘤活性与剂量和浓度相关，50%抑制浓度（IC50）范围为1.7至14.3微克/毫升，平均±标准差（SD）为8.4±4.6微克/毫升。新鲜手术脾细胞标本在48小时孵育中的IC50范围为0.34微克/毫升至>100微克/毫升，平均±SD为66.5±37.7微克/毫升。当比较同一患者的胃癌细胞和脾细胞对MKT-077的抗肿瘤活性时，该药物在癌细胞中浓度依赖性的抗肿瘤活性明显，而在脾细胞中未观察到明显的细胞毒性。在浓度为三十微克/毫升时，胃癌新鲜手术标本对MKT-077的敏感性高于脾细胞，P<0.05，差异有统计学意义。
使用新鲜手术标本证实了MKT-077具有选择性抗肿瘤活性，值得进一步研究。
