title: Combinations of tnp-470 or sr-4233 with antitumor alkylating-agents in emt-6 spheroids and monolayers.
abstract: EMT-6/Parent and EMT-6/CDDP and EMT-6/CTX in vivo alkylating agent resistant cells were grown as spheroids or as monolayers and their response to cis-diamminedichloroplatinum(II) or 4-hydroperoxycyclophosphamide exposure for 1 h alone or in combination with TNP-470 or SR-4233 was determined. When grown as spheroids, each of the three cell lines were less responsive to cis-diamminedichloroplatinum(II) and 4-hydroperoxycyclophosphamide exposure than when the cells were grown and drug-treated in monolayer. The hypoxic cell selective cytotoxic agent SR-4233 was additive in cytotoxicity with the antitumor alkylating agents in both the monolayer and spheroid cultures as determined by isobologram analysis. The antiangiogenic agent TNP-470 was synergistic in cytotoxicity in combination with cis-diammedichloroplatinum in each of the three cell lines when the cells were grown in monolayer and was additive in cytotoxicity with cis-diamminedichloroplatinum(II) when the cells were grown as spheroids. The combination of TNP-470 and 4-hydroperoxycyclophosphamide resulted in additive cytotoxicity toward both monolayer cultures and spheroids. Thus, co-exposure with TNP-470 or SR-4233 increased the cytotoxicity of the antitumor alkylating agents in both the parental and drug resistant cells grown as monolayers or spheroids.
authors.affiliation: DANA FARBER CANC INST,BOSTON,MA 02115. JOINT CTR RADIAT THERAPY,BOSTON,MA 02115.
authors.forename: S
authors.initials: S
authors.lastname: Holden
authors.forename: B
authors.initials: B
authors.lastname: Teicher