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Cancer Cell International

, 13:33

First Online: 10 April 2013Received: 20 November 2012Accepted: 07 March 2013

Abstract

BackgroundOvarian 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.

MethodsChemosensitivity 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.

ResultsAll 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.

ConclusionsThe 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.

KeywordsPrimary ovarian cancer cells Microtubule-interacting agents Cell cycle analyses Chemosensitivity Epothilone B Electronic supplementary materialThe online version of this article doi:10.1186-1475-2867-13-33 contains supplementary material, which is available to authorized users.

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Autor: Ilenia Pellicciotta - Chia-Ping Huang Yang - Charis A Venditti - Gary L Goldberg - Shohreh Shahabi

Fuente: https://link.springer.com/







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