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

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 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 multicellular 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.