Cisplatin, doxorubicin and paclitaxel induce mdr1 gene transcription in ovarian cancer cell lines.
The clinical observation of the multidrug resistance (MDR) phenotype is often associated with overexpression of the mdrl gene, in particular with respect to ovarian cancer. However, until now the mdrl-inducing potential of commonly used antineoplastics has been only incompletely explored. We performed short-term cultures of six ovarian cancer cell lines (MZOV4, EF027, SKOV3, OAW42, OTN14, MZOV20) exposed to either blank medium or cisplatin, doxorubicin or paclitaxel at concentrations related to the clinically achievable plasma peak concentration. A highly specific quantitative real-time RT-PCR was used to detect the Mdr1 transcripts. Mdrl mRNA contents were calibrated in relation to coamplified GAPDH mRNA. Mdrl mRNA was detectable in each cell line. In 13 out of 18 assays (72%) the specific anticancer drug being tested induced mdr1 transcription. No decrease in mdr1 mRNA concentration was observed. Our data suggest that mdr1 induction by antineoplastics is one of the reasons for failure of ovarian cancer therapy but may vary individually.
Schöndorf
Thomas
T
Department of Gynecology and Obstetrics, University of Cologne, Kerpener Strasse 34, 50931 Köln, Germany. thomas.schoendorf@medizin.uni-koeln.de
Neumann
Rainer
R
Benz
Carolin
C
Becker
Martina
M
Riffelmann
Marion
M
Göhring
Uwe-Jochen
UJ
Sartorius
Judith
J
von König
Carl-Heinz Wirsing
CH
Breidenbach
Martina
M
Valter
Markus M
MM
Hoopmann
Markus
M
Di Nicolantonio
Federica
F
Kurbacher
Christian M
CM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D017931:DNA Primers; D012333:RNA, Messenger; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin