title: Expression of organic anion-transporting polypeptides 1B1 and 1B3 in ovarian cancer cells: relevance for paclitaxel transport.
abstract: OBJECTIVE
  Ovarian cancer remains a deadly malignancy because most patients develop recurrent disease that is resistant to chemotherapy. Organic anion-transporting polypeptides (OATPs) mediate the uptake of clinically important drugs thereby effecting intracellular drug accumulation. In this study, we investigated whether OATPs may also contribute to paclitaxel transport in estrogen-responsive and estrogen-independent ovarian carcinoma cell lines and tumor tissue.
  
  
  METHODS
  Expression of all 11 human OATPs in human ovarian cancer tissue samples and in the ovarian carcinoma cell lines OVCAR-3 and SK-OV-3 was investigated using real-time RT-PCR. Kinetic analysis of paclitaxel uptake was characterized in both cell lines and in OATP-transfected Xenopus laevis oocytes. Cytotoxicity of paclitaxel in OVCAR-3, SK-OV-3 and OATP1B1- and OATP1B3-transfected SK-OV-3 cells was performed using the CellTiter-Glo assay.
  
  
  RESULTS
  OATP1B1 and OATP1B3 are active paclitaxel transporters in transfected X. laevis oocytes. Real-time RT-PCR analysis revealed expression of both OATPs in human ovarian cancer tissue specimens and in cancer cell lines. The higher mRNA levels for OATP1B1 and OATP1B3 found in SK-OV-3 cells correlated with higher initial uptake rates for paclitaxel. In addition, cytotoxicity studies with OATP1B1- and OATP1B3-transfected SK-OV-3 cells demonstrated lower IC(50) values compared to cells transfected with the empty vector.
  
  
  CONCLUSIONS
  Our results revealed OATP1B1 and OATP1B3 as high-affinity paclitaxel transporters expressed in ovarian cancer cell lines and tumor tissues, suggesting a role for these polypeptides in the disposition of paclitaxel during therapy.
authors: Department of Pathophysiology, Medical University of Vienna, 1090 Vienna, Austria.
authors: Martin
authors: M
authors: Svoboda
authors: Katrin
authors: K
authors: Wlcek
authors: Barbara
authors: B
authors: Taferner
authors: Steffen
authors: S
authors: Hering
authors: Bruno
authors: B
authors: Stieger
authors: Dan
authors: D
authors: Tong
authors: Robert
authors: R
authors: Zeillinger
authors: Theresia
authors: T
authors: Thalhammer
authors: Walter
authors: W
authors: Jäger
mesh_terms: D000328:Adult; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D027381:Liver-Specific Organic Anion Transporter 1; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism*; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D017239:Paclitaxel / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D014982:Xenopus laevis
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D027381:Liver-Specific Organic Anion Transporter 1; D009363:Neoplasm Proteins; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D029362:Organic Anion Transporters, Sodium-Independent; D012333:RNA, Messenger; D011994:Recombinant Proteins; C503999:SLCO1B1 protein, human; C421209:SLCO1B3 protein, human; D000074542:Solute Carrier Organic Anion Transporter Family Member 1B3; D017239:Paclitaxel