Cyclosporin A and its analogues as modifiers of adriamycin and vincristine resistance in a multi-drug resistant human lung cancer cell line.

Pr Twentyman,Ne Fox,Djg White

doi:10.1038/bjc.1987.153

Abstract

Cyclosporin A and its analogues as modifiers of adriamycin and vincristine resistance in a multi-drug resistant human lung cancer cell line

Highlights

The derivation and characteristics of a multi-drug resistant variant (NCI-H69/LX4) of the human small cell lung cancer line NCI-H69/P have been previously described (Twentyman et al, 1986b)
The variant line was obtained by growth of cells in vitro in increasing concentrations of adriamycin
Two replicate dishes were used in the control growth and a single dish at each of 6 or 7 different drug doses used to establish the drug response curve

Summary

SHORT COMMUNICATION

The problem of pleiotropic drug resistance in cancer chemotherapy may be tackled in a number of ways. One of these involves the use of additional chemical agents (resistance modifiers) which partially or fully restore cytotoxic drug sensitivity to resistant cells. In this paper we describe studies carried out using a multi-drug resistant variant of a human small cell lung cancer line. The derivation and characteristics of a multi-drug resistant variant (NCI-H69/LX4) of the human small cell lung cancer line NCI-H69/P have been previously described (Twentyman et al, 1986b). The cyclosporins were initially dissolved in absolute ethanol They were diluted 1: 10 in medium and added to 5 ml of growth medium in a volume of 50p1, thereby producing a final ethanol concentration of 0.1%. Sensitisation of H69/LX4 cells to ADM is clearly dependent upon the dose of CsA (Table II) but some sensitisation was still seen at 0.5-1 4ug ml1-I CsA

Dose of

Findings

The ability of CsA analogues to overcome ADM