Influence of chloroquine and lidocaine on retention and cytotoxic effects of [131I]EGF: studies on cultured glioma cells.
Targeting of toxic substances to the epidermal growth factor, EGF, receptor might be an attractive therapeutic approach because of the increased receptor-expression in some human tumours such as, for example, malignant gliomas and squamous lung carcinomas. Radiation effects of [131I]EGF on human malignant glioma cells growing as monolayers were analysed in this study. The cells were, in all cases, incubated for 25 min with about 350 kBq/ml [131I]EGF, which gave a total binding of 3.2-3.5 kBq/10(5) cells. The rapid release of activity from the cells caused by the normal degradation of EGF was inhibited by incubation with 30 microM chloroquine or 5 mM lidocaine added to the cell culture medium. These substances are, at these concentrations, known to inhibit proteolytic processes in lysosomes. No effects of the inhibitors alone were observed on cell growth and clonogenic survival. Inhibition of EGF degradation by chloroquine or lidocaine resulted in a significantly prolonged association of 131I with the test cells. About 70% of the initially bound radioactivity remained in the cells giving, after 6 h, a binding of 2.1-2.5 kBq/10(5) cells. A 6 h exposure to the radiation from 131I decays, mediated mainly by specifically bound EGF, gave a survival value of about 50%. Such an effect corresponds to a treatment of 2.5 Gy 60Co gamma-radiation. This is promising considering that, when monolayers are applied, only a very small fraction of the released energy from the 131I decays is deposited in the cells. Effects from non-receptor bound [131I]EGF were analysed after presaturation of the receptors with non-radioactive EGF, and gave no or very small changes in survival.
Capala
J
J
Department of Radiation Sciences, Uppsala University, Sweden.
Carlsson
J
J
D002478:Cells, Cultured; D002738:Chloroquine / Q000627:therapeutic use*; D004815:Epidermal Growth Factor / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005910:Glioma / Q000532:radiotherapy*; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008012:Lidocaine / Q000627:therapeutic use*
D007457:Iodine Radioisotopes; D004815:Epidermal Growth Factor; D002738:Chloroquine; D008012:Lidocaine