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Open Access Primary research

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

Ilenia Pellicciotta1, Chia-Ping Huang Yang23, Charis A Venditti4, Gary L Goldberg2 and Shohreh Shahabi24*

Author Affiliations

1 Department of Radiation Oncology, New York University College of Medicine, New York, NY 10016, USA

2 Department of Obstetrics & Gynecology and Women’s Health, Division of Gynecologic Oncology, Montefiore Medical Center, the Albert Einstein College of Medicine and the Albert Einstein Cancer Center, Bronx, New York, NY 10461, USA

3 Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA

4 Department of Obstetrics, Gynecology, and Reproductive Biology, Danbury Hospital, 24 Hospital Avenue, Danbury, CT 06810, USA

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Cancer Cell International 2013, 13:33  doi:10.1186/1475-2867-13-33

Published: 10 April 2013

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.

Keywords:
Primary ovarian cancer cells; Microtubule-interacting agents; Cell cycle analyses; Chemosensitivity; Epothilone B