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Chemotherapy in pregnancy: exploratory study of the effects of paclitaxel on the expression of placental drug transporters
- Source :
- Investigational New Drugs, Investigational New Drugs, Springer Verlag, 2019, 37 (5), pp.1075-1085. ⟨10.1007/s10637-018-0677-7⟩
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- International audience; 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.
- Subjects :
- Adult
0301 basic medicine
ATP Binding Cassette Transporter, Subfamily B
Paclitaxel
Abcg2
Placenta
medicine.medical_treatment
[SDV.CAN]Life Sciences [q-bio]/Cancer
[SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics
Pharmacology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Pregnancy
In vivo
Neoplasms
Drug transporters
ATP Binding Cassette Transporter, Subfamily G, Member 2
Humans
Placental perfusion
Medicine
Pharmacology (medical)
Cancer
Cisplatin
Chemotherapy
biology
business.industry
Trophoblast
[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology
Prognosis
Antineoplastic Agents, Phytogenic
Neoplasm Proteins
3. Good health
Gene Expression Regulation, Neoplastic
030104 developmental biology
medicine.anatomical_structure
Oncology
chemistry
030220 oncology & carcinogenesis
biology.protein
Female
business
Pregnancy Complications, Neoplastic
Ex vivo
medicine.drug
Subjects
Details
- ISSN :
- 15730646 and 01676997
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Investigational New Drugs
- Accession number :
- edsair.doi.dedup.....6aa475047d4ad089ac1d40ac37ba459c