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Investigational New Drugs

, Volume 37, Issue 5, pp 1075–1085 | Cite as

Chemotherapy in pregnancy: exploratory study of the effects of paclitaxel on the expression of placental drug transporters

  • Paul BerveillerEmail author
  • Olivier Mir
  • Séverine A. Degrelle
  • Vassilis Tsatsaris
  • Lise Selleret
  • Jean Guibourdenche
  • Danièle Evain-Brion
  • Thierry Fournier
  • Sophie Gil
PRECLINICAL STUDIES
  • 156 Downloads

Summary

Introduction The use of paclitaxel in pregnant cancer patients is feasible in terms of fetal safety, but little is known about the effects of paclitaxel on the placenta. Using three experimental models, we aimed to assess the effects of paclitaxel on the expression of placental drug transporters. Methods In the in vitro model (human primary trophoblast culture), trophoblasts were isolated from normal term placentas and subsequently exposed to paclitaxel. The transcriptional regulation of 84 genes encoding for drug transporters, and the protein expression of ABCB1/P-gp and ABCG2/BCRP were assessed. In the in vivo model, placental tissues isolated from pregnant cancer patients treated with paclitaxel were analyzed to assess the protein expression of ABCB1/P-gp and ABCG2/BCRP. The same parameters were assessed in extracts from human placental cotyledons perfused ex vivo with paclitaxel. Results In the in vitro model, the expression of twelve drug-transporters genes was found to be significantly down-regulated after exposure to paclitaxel, including ABCC10, SLC28A3, SLC29A2, and ATP7B (involved in the transport of taxanes, antimetabolites, and cisplatin, respectively). The protein expression of ABCB1/P-gp increased by 1.3-fold after paclitaxel administration. Finally, the protein expression of ABCB1/P-gp and ABCG2/BCRP was higher in cotyledons from mothers treated with multiple doses of paclitaxel during pregnancy than in cotyledons perfused with a single dose of paclitaxel. Discussion Paclitaxel modulates the expression of placental drug transporters involved in the disposition of various anticancer agents. Further studies will be needed to assess the impact of repeated or prolonged exposure to paclitaxel on the expression and function of placental drug transporters.

Keywords

Cancer Pregnancy Placenta Paclitaxel Trophoblast Drug transporters Placental perfusion 

Notes

Acknowledgements

The authors wish to thank Ms. Helen Shriver for her help in the manuscript preparation. The authors also wish to thank Mrs. Christelle Simasotchi (PremUp Foundation – Université Paris Descartes) for her contribution in the study.

Funding

This work was supported by INSERM (Institut National de la Santé et de la Recherche Médicale).

Compliance with ethical standards

Conflict of interest

Dr. Berveiller declares that he has no conflict of interest.

Dr. Mir has acted as consultant for Astra-Zeeneca, Amgen, Bayer Healthcare, Blueprint Medicines, Bristol-Myers Squibb, Eli-Lilly, Incyte, Ipsen, Lundbeck, Novartis, Pfizer, PharmaMar, Roche, Servier and Vifor Pharma.

Dr. Degrelle declares that she has no conflict of interest.

Pr. Tsatsaris declares that he has no conflict of interest.

Dr. Selleret declares that she has no conflict of interest.

Pr. Guibourdenche declares that he has no conflict of interest.

Dr. Evain-Brion declares that she has no conflict of interest.

Dr. Fournier declares that he has no conflict of interest.

Pr. Gil declares that she has no conflict of interest.

Ethical approval

All procedures performed in studies involving our patients were in accordance with the ethical standards of the Local Ethic Committee (CPP, Paris Cochin, N°18–05, France) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in our study.

Supplementary material

10637_2018_677_MOESM1_ESM.docx (77 kb)
ESM 1 (DOCX 76 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Paul Berveiller
    • 1
    • 2
    • 3
    Email author
  • Olivier Mir
    • 4
  • Séverine A. Degrelle
    • 1
    • 2
  • Vassilis Tsatsaris
    • 1
    • 2
    • 5
    • 6
  • Lise Selleret
    • 7
  • Jean Guibourdenche
    • 8
  • Danièle Evain-Brion
    • 1
    • 2
    • 6
  • Thierry Fournier
    • 1
    • 2
    • 6
  • Sophie Gil
    • 1
    • 2
    • 6
  1. 1.INSERM, UMR-S1139ParisFrance
  2. 2.Université Paris Descartes, Sorbonne Paris CitéParisFrance
  3. 3.Department of Gynecology and ObstetricsCentre Hospitalier Intercommunal de Poissy Saint GermainPoissyFrance
  4. 4.Department of Cancer MedicineGustave Roussy Cancer CampusVillejuifFrance
  5. 5.Department of Obstetrics, Port-Royal MaternityCochin Teaching Hospital, Assistance Publique – Hôpitaux de ParisParisFrance
  6. 6.PremUp FoundationParisFrance
  7. 7.Department of Obstetrics and GynecologyTenon Teaching Hospital, Assistance Publique – Hôpitaux de ParisParisFrance
  8. 8.Department of Hormonal BiologyCochin Teaching Hospital, Assistance Publique – Hôpitaux de ParisParisFrance

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