Expression of organic anion-transporting polypeptides 1B1 and 1B3 in ovarian cancer cells: relevance for paclitaxel transport

Biomed Pharmacother. 2011 Sep;65(6):417-26. doi: 10.1016/j.biopha.2011.04.031. Epub 2011 Jun 12.


Purpose: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antineoplastic Agents, Phytogenic / metabolism*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Biological Transport
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inhibitory Concentration 50
  • Kinetics
  • Liver-Specific Organic Anion Transporter 1
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Oocytes / metabolism
  • Organic Anion Transport Protein 1 / genetics
  • Organic Anion Transport Protein 1 / metabolism*
  • Organic Anion Transporters / genetics
  • Organic Anion Transporters / metabolism*
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Organic Anion Transporters, Sodium-Independent / metabolism*
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Paclitaxel / metabolism*
  • Paclitaxel / pharmacology
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Xenopus laevis


  • Antineoplastic Agents, Phytogenic
  • Liver-Specific Organic Anion Transporter 1
  • Neoplasm Proteins
  • Organic Anion Transport Protein 1
  • Organic Anion Transporters
  • Organic Anion Transporters, Sodium-Independent
  • RNA, Messenger
  • Recombinant Proteins
  • SLCO1B1 protein, human
  • SLCO1B3 protein, human
  • Solute Carrier Organic Anion Transporter Family Member 1B3
  • Paclitaxel