Biomol Ther.  2014 Jan;22(1):68-72.

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

• Lee NY
• Lee HE
• Kang YS

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 Km of 168 microM and 371 microM in TR-TBT 18d-1 and TR-TBT 18d-2, respectively. [3H]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 [3H]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.

Keyword

Paclitaxel; Pregnancy; Syncytiotrophoblast; TR-TBT cells; Blood-placental barrier; P-glycoprotein

MeSH Terms

Animals
Anions
Breast
Cell Line
Cyclosporine
Drug Therapy
Female
Fetus
Humans
Ovarian Neoplasms
P-Glycoprotein*
Paclitaxel*
Placenta
Pregnancy
Pregnant Women
Rats
RNA, Messenger
Trophoblasts*
Verapamil
Anions
Cyclosporine
P-Glycoprotein
Paclitaxel
RNA, Messenger
Verapamil