Expression of P-glycoprotein and in vitro or in vivo resistance to doxorubicin and cisplatin in breast and ovarian cancers.
The expression of P-glycoprotein (P-gp) was studied by immunocytohistochemistry, using the C219 monoclonal antibody, in 39 locally advanced breast cancers and 20 ovarian cancers from previously untreated patients. P-gp was expressed in 46 and 35% of breast and ovarian tumours, respectively. A significant association was observed in both tumour types between P-gp expression and in vitro resistance to doxorubicin. We also observed a higher clinical response rate to doxorubicin +/- vincristine in patients with breast cancers not expressing P-gp. Conversely, no correlation was found between P-gp expression and in vitro resistance to cisplatin or in vivo response to cisplatin +/- cyclophosphamide treatment in ovarian cancers. Our results support the relevance of P-gp expression as a specific indicator of resistance to certain drugs, such as doxorubicin and vincristine, involved in the phenomenon of multidrug resistance in breast and ovarian cancer cells.
Veneroni
S
S
Divisione di Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Zaffaroni
N
N
Daidone
M G
MG
Benini
E
E
Villa
R
R
Silvestrini
R
R
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D002945:Cisplatin / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D002945:Cisplatin