Sensitivities of monolayers and spheroids of the human bladder cancer cell line MGH-U1 to the drugs used for intravesical chemotherapy

Abstract

The in vitro cytotoxicities of the four drugs most frequently used for intravesical chemotherapy (Adriamycin, epodyl, mitomycin C, Thiotepa) and epirubicin were compared using monolayers and multicellular tumor spheroids of the human bladder cancer cell line, MGH-U1. Adriamycin and epirubicin were most cytotoxic against monolayer cultures, whereas mitomycin C killed more cells in spheroids. Epodyl was least cytotoxic against both two- and three-dimensional cultures. Thiotepa was the only drug more cytotoxic to three- than two-dimensional cultures. Topographic analysis of bromodeoxyuridine-stained nuclei using image analysis indicated that Adriamycin selectively removed or killed superficial cells in multicellular tumor spheroids, but had little effect on DNA synthesis within the spheroids. In contrast Thiotepa killed cells throughout the spheroids. These in vitro data appear to reflect clinical experience using intravesical chemotherapy to treat superficial bladder cancer.