Doxorubicin induced expression of P-glycoprotein in a canine osteosarcoma cell line.
Canine and human osteosarcoma are very similar with respect to clinical presentation, radiological and histopathological features, metastatic rate and pattern and response to therapy. For these reasons, canine osteosarcoma is a useful intermediate model for the disease in humans. Overexpression of P-glycoprotein, the product of the MDR1 gene, is the most important predictor of an adverse clinical course in human patients with osteosarcoma. Exposure of canine osteosarcoma cells to doxorubicin resulted in overexpression of MDR1 mRNA and P-glycoprotein. Furthermore, these cells failed to accumulate doxorubicin intracellularly and were less sensitive to vincristine-induced cytotoxicity as compared to parental cells.
Mealey
K L
KL
Department of Veterinary Physiology and Pharmacology, Texas A&M University, College of Veterinary Medicine, College Station 77843, USA.
Barhoumi
R
R
Rogers
K
K
Kochevar
D T
DT
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000378:metabolism / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001859:Bone Neoplasms / Q000378:metabolism*; D004285:Dogs; D004317:Doxorubicin / Q000378:metabolism / Q000494:pharmacology*; D018432:Drug Resistance, Multiple; D015151:Immunoblotting; D009363:Neoplasm Proteins / Q000187:drug effects* / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D009363:Neoplasm Proteins; D014750:Vincristine; D004317:Doxorubicin