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.
Highlights
Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world
We have studied cell cycle analyses of primary ovarian cancer cells treated with Taxol, epothilone B (EpoB) and discodermolide, and compared it to that of immortalized ovarian cancer cell lines SKOV3 and Hey - commonly used for ovarian cancer studies
In this report we describe the isolation and characterization of primary human ovarian cancer cell lines derived from untreated patients diagnosed with histologically confirmed epithelial ovarian cancer
Summary
Ovarian cancer constitutes nearly 4% of all cancers among women and is the leading cause of death from gynecologic malignancies in the Western world. We describe the generation and characterization of primary ovarian cancer cells derived from ascites fluids of patients with epithelial ovarian cancer. We describe here a modified protocol to isolate and grow in vitro cultures of primary ovarian cancer cells derived from ascites fluids of patients with histologically confirmed epithelial ovarian cancer. We have established a series of primary ovarian cancer cell cultures from the ascites of patients with ovarian carcinoma and have characterized them while still at an early stage in culture. We have studied their growth characteristics, histochemical properties, and used them as a model to study in vitro sensitivity to microtubule interacting agents. It has been widely reported that Taxol exerts cytotoxic effects to primary ovarian cancer cells [5], this is the first time to the best of our knowledge, that the sensitivity to EpoB and discodermolide is described
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