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Induction of MDR1-gene expression by antineoplastic agents in ovarian cancer cell lines
Thomas Schöndorf1, Christian M Kurbacher, Uwe-Jochen Göhring
1Department of Gynecology and Obstetrics, University of Cologne, Germany. thomas.schoendorf@medizin.uni-koeln.de
Background:
Development of resistance to anticancer drugs is a major concern in clinical oncology and might be particularly involved in the secondary treatment failure frequently seen in ovarian cancer. Clinical observation of the multidrug resistance (MDR) phenotype is often associated with overexpression of the mdr1-gene. However, until now the mdr1-inducing potential of commonly used antineoplastics has been only incompletely explored.
Materials And Methods:
We perfomed short-term cultures of 7 established ovarian cancer cell lines exposed to either blank medium or one of three single anticancer drugs (cisplatin, doxorubicin, paclitaxel) at concentrations related to the clinically achievable plasma peak concentration. Mdr1-transcripts were detected using the highly specific quantitative real time RT-PCR. To calibrate each approach, mdr1-mRNA content was calculated in relation to co-amplified GAPDH-mRNA.
Results:
Mdr1-mRNA was detectable in each cell line. In 13 assays (62%) the specific anticancer drug being tested induced mdr1-transcription. No decrease in mdr1-mRNA concentration was observed. The method described here is easy to perform and could be of striking value in predicting the development of tumor chemoresistance.
Conclusion:
Our data indicate that mdr1-induction by antineoplastics is one of the reasons for failure of ovarian cancer therapy but may vary from one individual to another.
Insights
Anticancer drugs can induce mdr1-gene transcription, contributing to multidrug resistance (MDR) and treatment failure in ovarian cancer. This induction varies between patients, highlighting the need for personalized therapy strategies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Anticancer drug resistance is a significant challenge in oncology, particularly in ovarian cancer treatment.
- The multidrug resistance (MDR) phenotype is often linked to mdr1-gene overexpression.
- The capacity of common antineoplastics to induce mdr1 has not been fully investigated.
Purpose of the Study:
- To investigate the mdr1-inducing potential of commonly used anticancer drugs in ovarian cancer cell lines.
- To explore the role of mdr1-gene induction in secondary treatment failure.
Main Methods:
- Short-term cultures of 7 ovarian cancer cell lines were exposed to cisplatin, doxorubicin, or paclitaxel.
- Quantitative real-time RT-PCR was used to detect and quantify mdr1-transcripts.
- GAPDH mRNA was used for normalization of mdr1-mRNA levels.
Main Results:
- Mdr1-mRNA was detected in all tested ovarian cancer cell lines.
- The tested anticancer drugs induced mdr1-transcription in 62% of the assays.
- No decrease in mdr1-mRNA levels was observed during the experiments.
Conclusions:
- Antineoplastic drugs can induce mdr1, contributing to ovarian cancer therapy failure.
- The extent of mdr1-induction by anticancer drugs can differ among individuals.
- The described method may aid in predicting tumor chemoresistance development.