Evaluation of the potential of transferrin-adriamycin conjugates in the treatment of bladder cancer.
OBJECTIVE
To assess the ability of a transferrin-adriamycin conjugate (Tf-ADR) to target transferrin receptor (TfR)-positive cancer cells selectively and to overcome drug resistance in bladder cancer cell lines.


METHODS
Two paired sets of cell lines were used: the first was Chinese hamster ovary (CHO) cells (TfR-negative TRVb cells, as a model for normal resting cells, and TRVb-1 cells which were transfected with human TfR), and the second was a pair of bladder cancer cell lines (ADR-sensitive MGH-U1 cells and ADR-resistant MGH-U1R cells). Cell survival curves were determined after treatment with ADR, Tf and Tf-ADR.


RESULTS
MGH-U1, TRVb and TRVb-1 cells required similar concentrations of ADR and Tf-ADR for 50% inhibition of growth; MGH-U1R cells were resistant to both ADR and TF-ADR.


CONCLUSIONS
Tf-ADR did not prevent toxicity to the TfR-negative cells nor did it overcome the resistance of the ADR-resistant cells. These results imply that Tf-ADR does not provide a better cytotoxic drug delivery system for the treatment of bladder cancer.
Royal Brisbane Hospital, Queensland, Australia.
J
J
Munns
J
J
Yaxley
J
J
Coomer
M F
MF
Lavin
R A
RA
Gardiner
D
D
Watters
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D002470:Cell Survival; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage*; D004337:Drug Carriers; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D006801:Humans; D009368:Neoplasm Transplantation; D014168:Transferrin / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D004338:Drug Combinations; D014168:Transferrin; D004317:Doxorubicin