Cisplatin, Doxorubicin and Paclitaxel Induce mdr1 Gene Transcription in Ovarian Cancer Cell Lines

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Abstract
The clinical observation of the multidrug resistance (MDR) phenotype is often associated with overexpression of the mdr1 gene, in particular with respect to ovarian cancer. However, until now the mdr1-inducing potential of commonly used antineoplastics has been only incompletely explored. We performed short-term cultures of six ovarian cancer cell lines (MZOV4, EFO27, 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. Mdr1 mRNA contents were calibrated in relation to coamplified GAPDH mRNA. Mdr1 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.