Response to microtubule-interacting agents in primary epithelial ovarian cancer cells

Ilenia Pellicciotta, Chia-Ping H. Yang, Charis A. Venditti, Gary L. Goldberg, Shohreh Shahabi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. Standard first line adjuvant chemotherapy treatments include Paclitaxel (Taxol) and platinum-based agents. Taxol, epothilone B (EpoB) and discodermolide belong to a family of anti-neoplastic agents that specifically interferes with microtubules and arrests cells in the G2/M phase of the cell cycle. Despite initial success with chemotherapy treatment, many patients relapse due to chemotherapy resistance. In vitro establishment of primary ovarian cancer cells provides a powerful tool for better understanding the mechanisms of ovarian cancer resistance. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer.Methods: Chemosensitivity of these cell lines to Taxol, EpoB and discodermolide was tested, and cell cycle analysis was compared to that of immortalized ovarian cancer cell lines SKOV3 and Hey. The relationship between drug resistance and αβ-tubulin and p53 status was also investigated.Results: All newly generated primary cancer cells were highly sensitive to the drugs. αβ-tubulin mutation was not found in any primary cell lines tested. However, one cell line that harbors p53 mutation at residue 72 (Arg to Pro) exhibits altered cell cycle profile in response to all drug treatments. Immortalized ovarian cancer cells respond differently to EpoB treatment when compared to primary ovarian cancer cells, and p53 polymorphism suggests clinical significance in the anti-tumor response in patients.Conclusions: The isolation and characterization of primary ovarian cancer cells from ovarian cancer patients' specimens contribute to further understanding the nature of drug resistance to microtubule interacting agents (MIAs) currently used in clinical settings.

Original languageEnglish (US)
Article number33
JournalCancer Cell International
Volume13
Issue number1
DOIs
StatePublished - Apr 10 2013

Fingerprint

Microtubules
Ovarian Neoplasms
Cell Line
Cell Cycle
Tubulin
Paclitaxel
Drug Resistance
Neoplasms
Ovarian epithelial cancer
Drug Therapy
Western World
Mutation
G2 Phase
Therapeutics
Adjuvant Chemotherapy
Platinum
Ascites
Pharmaceutical Preparations
Cell Division
Cause of Death

Keywords

  • Cell cycle analyses
  • Chemosensitivity
  • Epothilone B
  • Microtubule-interacting agents
  • Primary ovarian cancer cells

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Genetics

Cite this

Response to microtubule-interacting agents in primary epithelial ovarian cancer cells. / Pellicciotta, Ilenia; Yang, Chia-Ping H.; Venditti, Charis A.; Goldberg, Gary L.; Shahabi, Shohreh.

In: Cancer Cell International, Vol. 13, No. 1, 33, 10.04.2013.

Research output: Contribution to journalArticle

Pellicciotta, Ilenia ; Yang, Chia-Ping H. ; Venditti, Charis A. ; Goldberg, Gary L. ; Shahabi, Shohreh. / Response to microtubule-interacting agents in primary epithelial ovarian cancer cells. In: Cancer Cell International. 2013 ; Vol. 13, No. 1.
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