Drug Resistance of Human Glioma Cell Lines in Culture — The Role of Membrane Transport
In animal tumour models resistance to adriamycin (ADR) and vincristine (VCR) has been shown to be associated with an energy-dependent cellular drug efflux mechanism which can be inhibited by calcium antagonists such as verapamil. The aim of this study is to establish the relevance of these data to human tumours. Our previous studies with human glioma cell lines have identified one cell line (MCF) sensitive to both ADR and VCR, and another (UVW) resistant to both drugs. Cell monolayers in soda glass tubes were exposed to radioactively labelled drug, cooled rapidly (0–5°C) and washed. Drug-free medium was added, the cells were incubated and intracellular drug determined by measuring label released into the medium. The plateau level of drug was determined for each cell line in the presence (6mM glucose) and absence (no glucose, 10mM NaN3) of an energy source. For ADR the removal of the energy source made no apparent difference to the plateau drug level of MCF, however for UVW plateau drug level rose by at least 300%. A similar increase in plateau drug level was observed in UVW when cells were exposed to verapamil in the presence of energy. For VCR, a 100% increase in plateau drug level of UVW cells was noted when the energy source was removed. These preliminary data suggest that for certain drugs resistant human tumour cells may possess a similar energy-dependent drug efflux mechanism to that seen in animal tumour models and this may be reversed with verapamil. Studies with other cell lines, including lung carcinoma, are now in progress.