A cell line with unusual characteristics from an ovarian carcinoma patient: modulation of sensitivity to antitumour drugs.
A cell line (GZL-8) was established by cloning from ascitic fluid of an untreated ovarian carcinoma patient. The cells grew rapidly, accumulated lipids and showed chromosomal alterations. One of the marker chromosomes showed characteristics of a Y-like chromosome. This unusual finding was confirmed by DNA hybridisation using specific probes to the Y chromosome. The cells stained with fluorescent antibodies to desmoplakin and cytokeratins 8, 18, 19, and weakly with vimentin but not with desmin. The presence of epithelial membrane antigen, human milk fat globulin, alpha-lactalbumin, alpha-fetoprotein, placental alkaline phosphatase and oestrogen receptor-related antigen was demonstrated by indirect immunoperoxidase staining, but no CA-125 antigen could be detected. The cells showed positive reaction with antibodies to P-glycoprotein. The function of the P-glycoprotein transport system was demonstrated by the rhodamine-123 release test. The cells were initially responsive to doxorubicin, and to high concentrations of cisplatin. Growth inhibition by doxorubicin, especially at low doses was enhanced by the addition of verapamil or tamoxifen. This was shown by the soft agar clonogenic assay, by direct cell counting and by the MTT reducing test. Our results show that combination between drug and sensitivity modulators may be of potential clinical value in ovarian cancer.
Basil & Gerald Felsenstein Medical Research Center, Tikva, Israel.
L
L
Wasserman
R
R
Aviram
H
H
Levavi
J
J
Ovadia
Y
Y
Shneyuor
A
A
Frisch
O
O
Blau
E
E
Beery
A
A
Novogrodsky
J
J
Nordenberg
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000230:Adenocarcinoma / Q000473:pathology*; D000951:Antigens, Neoplasm / Q000032:analysis; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D007621:Karyotyping; D008562:Membrane Glycoproteins / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D013629:Tamoxifen / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014998:Y Chromosome
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D013629:Tamoxifen; D004317:Doxorubicin; D014700:Verapamil; D002945:Cisplatin