Effect of combined chloroquine and mild hyperthermia on hybrid spheroids containing either HeLa or S91/6 mouse melanoma cells

Abstract

AbstractWe found no significant decrease in the colony forming ability (clonogenicity) of either HeLa or S91/6 melanoma cells in hybrid spheroids incubated for 24 hr at 37°C with up to 30 μM chloroquine, nor for incubations of up to 9 hr at either 37 or 41°C with 30 μM chloroquine. Incubation for 24 hr at 41°C with chloroquine caused spheroids to disintegrate. When heating was applied to hybrid spheroids intermittently for 3 hr at the beginning and at the end of a 24 hr period of incubation with 30 μM chloroquine, there was no effect on HeLa cells but there was a highly significant decrease in the clonogenicity of S91/6 melanoma cells. Short‐term treatment (3 hr) with a combination of mild hyperthermia and 30 μM chloroquine which is non‐toxic to unirradiated cells in hybrid spheroids is, nevertheless, effective in decreasing the clonogenicity of irradiated cells of both lines. A similar increase in radiation lethality [radiation potentiating factor (RPF) of about 1.6] was obtained in both HeLa and in S91/6 cells. RPFs did not change significantly after correction of survival curves for cellular multiplicity, nor were they different from those previously reported by us for these cell lines in two versions of dense suspension cultures. Since many cells from biopsies will not grow in conventional culture systems but will do so in hybrid spheroids, the finding of similar RPF values in both systems for cell lines which will grow under both conditions suggests that hybrid spheroids may be useful for radiopotentiation studies. © 1995 Wiley‐Liss, Inc.