Study of the Effects of Dispase in the Chemotherapy of Multicellular Tumour Spheroids of Small-cell Lung Carcinoma in Man

Abstract

Abstract Multicellular tumour spheroids (MTS), diameter 650 μm, 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.