Doxorubicin retention and chemoresistance in human mesothelioma cell lines.
Eight cell lines were established from the pleural effusion of 4 patients with malignant mesothelioma. The most sensitive (FCCMES-4) and the most resistant (FCCMES-2) mesothelioma cell lines had IC50 of 0.66 and 1.85 microM for doxorubicin in clonogenic assays, respectively. In comparison with murine leukemic P388 cells, mesothelioma cell lines were 7.5- to 21-fold more resistant to doxorubicin. Co-incubation with verapamil significantly increased doxorubicin retention in one of the cell lines (FCCMES-2) expressing P-glycoprotein in 16.8% of the cells. These results indicate that doxorubicin resistance may be intrinsic in refractory mesothelioma patients and P-glycoprotein-mediated drug efflux may be involved in resistance of some of the mesotheliomas.
Isobe
H
H
Department of Radiation Oncology, University of Miami Medical School, FL 33101.
Wellham
L
L
Sauerteig
A
A
Sridhar
K S
KS
Ramachandran
C
C
Krishan
A
A
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology; D008654:Mesothelioma / Q000188:drug therapy / Q000378:metabolism*; D016066:Pleural Effusion, Malignant / Q000473:pathology; D011003:Ploidies; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014700:Verapamil / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D004273:DNA, Neoplasm; D008562:Membrane Glycoproteins; D004317:Doxorubicin; D014700:Verapamil