P-glycoprotein expression in bladder cancer.
Multi-drug resistance is a phenomenon by which tumor cells express resistance to a variety of chemically unrelated chemotherapeutic drugs. The classical form of multi-drug resistance is mediated through the expression of P-glycoprotein, which acts as an energy dependent drug efflux pump. P-glycoprotein expression was evaluated in 29 cystectomy specimens from patients with bladder cancer with no prior exposure to chemotherapeutic drugs, and in bladder biopsies from 9 subjects before treatment with intravesical doxorubicin. Furthermore, the strategy of circumvention of P-glycoprotein-mediated resistance using the combination of doxorubicin and verapamil intravesically was tested in 5 patients. P-glycoprotein was expressed in 75% of the cystectomy specimens. In the doxorubicin treated patients no correlation was noted between P-glycoprotein expression on the initial tumors and subsequent response to doxorubicin. The pilot trial of verapamil and doxorubicin was well tolerated but did not suggest increased efficacy of this combination. P-glycoprotein can be expressed on bladder cancer cells without prior chemotherapy. The role of P-glycoprotein mediated multi-drug resistance in bladder cancer treatment failure remains to be defined.
Park
J
J
Department of Pathology, University of Michigan, Ann Arbor.
Shinohara
N
N
Liebert
M
M
Noto
L
L
Flint
A
A
Grossman
H B
HB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis* / Q000187:drug effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D010865:Pilot Projects; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism* / Q000517:prevention & control; D014700:Verapamil / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D004317:Doxorubicin; D014700:Verapamil