Matsuoka H, Okada M, Ishii N, Maeda S
Department of Surgery Division II, Kobe University School of Medicine, Hyogo, Japan.
J Pharm Pharmacol. 1998 Mar;50(3):285-90. doi: 10.1111/j.2042-7158.1998.tb06862.x.
Multicellular tumour spheroids (MTS), diameter 650 microm, from PC-6, SBC-1 and NCL-H60 small-cell lung carcinoma cell-lines in man were prepared by the liquid overlay culture method and used to study the influence of treatment with dispase (bacterial neutral protease from Bacillus polymyxa, 1000 units mL(-1)) on the effectiveness of carboplatin, as determined by colony-forming assay. When carboplatin alone was used on monolayers the curve of survival fraction against concentration was exponential in shape, indicating that the drug was active against the monolayer. When MTS were treated with medium concentrations (10(-5) and 10(-4) M) of carboplatin alone the survival fraction-concentration curve showed that the effectiveness of the treatment was less than that against the monolayer. On treatment of MTS with carboplatin and dispase the survival fraction-concentration curve was similar to that obtained for the monolayer and the survival fraction of the core of the MTS was also less than when carboplatin alone was used. These results imply that dispase dissolves the intercellular matrix of the MTS enabling enhanced infiltration of carboplatin into the core of the MTS. Dispase thus indirectly increases the effectiveness of carboplatin.
采用液体覆盖培养法制备了人源PC - 6、SBC - 1和NCL - H60小细胞肺癌细胞系的直径为650微米的多细胞肿瘤球体（MTS），并用于研究分散酶（来自多粘芽孢杆菌的细菌中性蛋白酶，1000单位 mL(-1)）处理对卡铂有效性的影响，通过集落形成试验测定。当单独将卡铂用于单层细胞时，存活分数与浓度的曲线呈指数形状，表明该药物对单层细胞有活性。当单独用中等浓度（10(-5)和10(-4) M）的卡铂处理MTS时，存活分数 - 浓度曲线表明该处理的有效性低于对单层细胞的有效性。当用卡铂和分散酶处理MTS时，存活分数 - 浓度曲线与单层细胞的相似，并且MTS核心的存活分数也低于单独使用卡铂时。这些结果表明，分散酶溶解了MTS的细胞间基质，使卡铂能更好地渗透到MTS的核心。因此，分散酶间接提高了卡铂的有效性。
