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Identification of P-Glycoprotein and Transport Mechanism of Paclitaxel in Syncytiotrophoblast Cells

Authors
Lee, Na-YoungLee, Ha-EunKang, Young-Sook
Issue Date
Jan-2014
Publisher
KOREAN SOC APPLIED PHARMACOLOGY
Keywords
Paclitaxel; Pregnancy; Syncytiotrophoblast; TR-TBT cells; Blood-placental barrier; P-glycoprotein
Citation
BIOMOLECULES & THERAPEUTICS, v.22, no.1, pp 68 - 72
Pages
5
Journal Title
BIOMOLECULES & THERAPEUTICS
Volume
22
Number
1
Start Page
68
End Page
72
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/10999
DOI
10.4062/biomolther.2013.105
ISSN
1976-9148
2005-4483
Abstract
When chemotherapy is administered during pregnancy, it is important to consider the fetus chemotherapy exposure, because it may lead to fetal consequences. Paclitaxel has become widely used in the metastatic and adjuvant settings for woman with cancer including breast and ovarian cancer. Therefore, we attempted to clarify the transport mechanisms of paclitaxel through blood-placenta barrier using rat conditionally immortalized syncytiotrophoblast cell lines (TR-TBTs). The uptake of paclitaxel was time- and temperature-dependent. Paclitaxel was eliminated about 50% from the cells within 30 min. The uptake of paclitaxel was saturable with K-m of 168 mu M and 371 mu M in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [H-3]Paclitaxel uptake was markedly inhibited by cyclosporine and verapamil, well-known substrates of P-glycoprotein (P-gp) transporter. However, several MRP substrates and organic anions had no effect on [H-3]paclitaxel uptake in TR-TBT cells. These results suggest that P-gp may be involved in paclitaxel transport at the placenta. TR-TBT cells expressed mRNA of P-gp. These findings are important for therapy of breast and ovarian cancer of pregnant women, and should be useful data in elucidating teratogenicity of paclitaxel during pregnancy.
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