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Establishment and characterization of a platinum- and paclitaxel-resistant high grade serous ovarian carcinoma cell line

  • Pang Ning Teng
  • , Nicholas W. Bateman
  • , Guisong Wang
  • , Tracy Litzi
  • , Brian E. Blanton
  • , Brian L. Hood
  • , Kelly A. Conrads
  • , Wei Ao
  • , Kate E. Oliver
  • , Kathleen M. Darcy
  • , William P. McGuire
  • , Keren Paz
  • , David Sidransky
  • , Chad A. Hamilton
  • , G. Larry Maxwell
  • , Thomas P. Conrads*
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

High grade serous ovarian cancer (HGSOC) patients have a high recurrence rate after surgery and adjuvant chemotherapy due to inherent or acquired drug resistance. Cell lines derived from HGSOC tumors that are resistant to chemotherapeutic agents represent useful pre-clinical models for drug discovery. Here, we describe establishment of a human ovarian carcinoma cell line, which we term WHIRC01, from a patient-derived mouse xenograft established from a chemorefractory HGSOC patient who did not respond to carboplatin and paclitaxel therapy. This newly derived cell line is platinum- and paclitaxel-resistant with cisplatin, carboplatin, and paclitaxel half-maximal lethal doses of 15, 130, and 20 µM, respectively. Molecular characterization of this cell line was performed using targeted DNA exome sequencing, transcriptomics (RNA-seq), and mass spectrometry-based proteomic analyses. Results from exomic sequencing revealed mutations in TP53 consistent with HGSOC. Transcriptomic and proteomic analyses of WHIRC01 showed high level of alpha-enolase and vimentin, which are associated with cell migration and epithelial–mesenchymal transition. WHIRC01 represents a chemorefractory human HGSOC cell line model with a comprehensive molecular profile to aid future investigations of drug resistance mechanisms and screening of chemotherapeutic agents.

Original languageEnglish
Pages (from-to)226-236
Number of pages11
JournalHuman Cell
Volume30
Issue number3
DOIs
StatePublished - 1 Jul 2017

Keywords

  • Cell line
  • High grade serous
  • Ovarian cancer
  • Paclitaxel resistance
  • Platinum resistance

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