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

Hum Cell. 2017 Jul;30(3):226-236. doi: 10.1007/s13577-017-0162-1. Epub 2017 Mar 1.

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.

Keywords: Cell line; High grade serous; Ovarian cancer; Paclitaxel resistance; Platinum resistance.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Carboplatin / pharmacology*
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery
  • Drug Resistance, Neoplasm*
  • Exome / genetics
  • Female
  • Gene Expression Profiling
  • Heterografts
  • Humans
  • Mice
  • Mutation
  • Neoplasm Staging
  • Neoplasm Transplantation
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / pathology*
  • Paclitaxel / pharmacology*
  • Proteomics
  • Tumor Suppressor Protein p53 / genetics

Substances

  • Antineoplastic Agents
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Carboplatin
  • Paclitaxel
  • Cisplatin