Expression of verapamil hypersensitivity in multidrug-resistant cells grown as multicellular spheroids

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Abstract
It is known that certain multidrug-resistant cell lines are hypersensitive to verapamil and to some other membrane-active agents. We examined the expression of verapamil hypersensitivity in a multidrug-resistant, verapamil-hypersensitive CHO cell line by cells grown in the form of multicellular spheroids. We found that although vincristine resistance is expressed at high levels in multi-cellular spheroids, we could not detect verapamil hypersensitivity when cells were grown in this form. Using a dry autoradiographic method to study the entry of [3H]-verapamil into the spheroids, we demonstrated that the lack of hypersensitivity was not due to incomplete drug penetration. We therefore propose that when hypersensitive multidrug-resistant cells are grown as three-dimensional spheroids, cellular interactions may modify the expression of verapamil hypersensitivity.