Introduction: For treatment of castration-refractory prostate cancer (CRPC) patients a systemic chemotherapy and a second line hormone therapy have been developed in the last years. The administration of the chemotherapeutic drug docetaxel in combination with prednisone given to patients with CRPC on the basis of its improved survival, pain reduction, PSA response, and quality of life is the state of the art treatment at the moment. However, many patients do not respond to docetaxel or develop a resistance during treatment. Due to the low overall response survival of the patient is prolonged just for a few months. Until now, not much of molecular characteristics for docetaxel resistance is known in prostate cancer. Therefore, the main aim of the study was the establishment and characterization of docetaxel resistant cell lines. For this reason we generated docetaxel resistent sub cell lines of DU-145 and PC3 cells, which are considered models for an advanced disease.

Methods: PC3 and DU-145 cells were treated with increasing concentrations of docetaxel (up to 12,5nM). The resistance of the newly established sub lines was determined by testing cell viability, proliferation, apoptosis, and cell cycle regulation with MTT, [3H]thymidine incorporation assay and FACS measurement, respectively.

Results: Treatment of parental PC3 and DU-145 cells with 12,5nM docetaxel up to 4 days leads to a significant decrease in cell viability. An increase of cleaved PARP protein after 48h for DU-145 and after 72h for PC3 cells could confirm this observation. In contrast to parental cells, the newly established PC3-DR and DU-145-DR docetaxel resistant cells have a different cell morphology. Treatment with docetaxel did not result in increased cPARP levels. Moreover, we could not detect a significant difference in proliferation, basal apoptosis and cell cycle regulation in a direct comparison between parental PC3 and PC3-DR cells. DU-145-DR cells showed a slight increase in apoptosis and a significant decrease in proliferation after docetaxel treatment. However, we still observed a higher viability compared to parental DU-145 cells treated with 12.5nM docetaxel.

Conclusions: The generated sub lines are less sensitive to docetaxel compared to the parental cells. However, DU-145-DR cells are more sensitive to docetaxel than PC3-DR cells. Taken together, we report on successful establishment and characterization of docetaxel-resistant PC3 and DU-145 cells. These cells represent a promising cellular model to investigate the responsible molecular mechanism for docetaxel resistance in prostate cancer cells in vitro.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1711. doi:10.1158/1538-7445.AM2011-1711