Cisplatin, doxorubicin and paclitaxel induce mdr1 gene transcription in ovarian cancer cell lines.

Thomas Schöndorf, Rainer Neumann, Carolin Benz, Martina Becker, Marion Riffelmann, Uwe Jochen Göhring, Judith Sartorius, Carl Heinz Wirsing von König, Martina Breidenbach, Markus M. Valter, Markus Hoopmann, Federica Di Nicolantonio, Christian M. Kurbacher

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33 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)111-116
Number of pages6
JournalRecent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer
Volume161
Publication statusPublished - 2003

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Ovarian Neoplasms
Doxorubicin
Cell Line
Messenger RNA
Antineoplastic Agents
Genes
Multiple Drug Resistance
Paclitaxel
Cisplatin
Real-Time Polymerase Chain Reaction
Observation
Phenotype
TP protocol
Pharmaceutical Preparations
Therapeutics

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Cisplatin, doxorubicin and paclitaxel induce mdr1 gene transcription in ovarian cancer cell lines. / Schöndorf, Thomas; Neumann, Rainer; Benz, Carolin; Becker, Martina; Riffelmann, Marion; Göhring, Uwe Jochen; Sartorius, Judith; von König, Carl Heinz Wirsing; Breidenbach, Martina; Valter, Markus M.; Hoopmann, Markus; Di Nicolantonio, Federica; Kurbacher, Christian M.

In: Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer, Vol. 161, 2003, p. 111-116.

Research output: Contribution to journal › Article

Schöndorf, T, Neumann, R, Benz, C, Becker, M, Riffelmann, M, Göhring, UJ, Sartorius, J, von König, CHW, Breidenbach, M, Valter, MM, Hoopmann, M, Di Nicolantonio, F & Kurbacher, CM 2003, 'Cisplatin, doxorubicin and paclitaxel induce mdr1 gene transcription in ovarian cancer cell lines.', Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer, vol. 161, pp. 111-116.
Schöndorf T, Neumann R, Benz C, Becker M, Riffelmann M, Göhring UJ et al. Cisplatin, doxorubicin and paclitaxel induce mdr1 gene transcription in ovarian cancer cell lines. Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer. 2003;161:111-116.
Schöndorf, Thomas ; Neumann, Rainer ; Benz, Carolin ; Becker, Martina ; Riffelmann, Marion ; Göhring, Uwe Jochen ; Sartorius, Judith ; von König, Carl Heinz Wirsing ; Breidenbach, Martina ; Valter, Markus M. ; Hoopmann, Markus ; Di Nicolantonio, Federica ; Kurbacher, Christian M. / Cisplatin, doxorubicin and paclitaxel induce mdr1 gene transcription in ovarian cancer cell lines. In: Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer. 2003 ; Vol. 161. pp. 111-116.
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AU - Göhring, Uwe Jochen

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AU - Breidenbach, Martina

AU - Valter, Markus M.

AU - Hoopmann, Markus

AU - Di Nicolantonio, Federica

AU - Kurbacher, Christian M.

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N2 - 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.

AB - 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.

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