Overcoming drug resistance in hormone-and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination
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Date
2010
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Abstract
Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose-and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array® (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated C3-fold change by the combination treatment. These results may be important in devising mechanism-based and targeted therapeutic strategies for prostate cancer, especially in devising combination therapy for drug resistant prostate cancers. © Springer Science+Business Media B.V. 2009.
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Keywords
Apoptosis , Cell Line, Tumor , DNA, Complementary , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm , Drug Therapy, Combination , Enzyme-Linked Immunosorbent Assay , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gossypol , Humans , Male , Prostatic Neoplasms , Taxoids , Time Factors , docetaxel , gossypol , complementary DNA , docetaxel , gossypol , taxoid , apoptosis , article , cancer cell culture , carcinogenesis , cell cycle regulation , cell metabolism , cell viability , concentration response , controlled study , cytotoxicity , DNA repair , dose time effect relation , down regulation , drug potentiation , gene expression profiling , human , human cell , male , polymerase chain reaction , prostate cancer , apoptosis , dose response , drug combination , drug effect , drug resistance , enzyme linked immunosorbent assay , gene expression regulation , genetics , physiology , prostate tumor , time , tumor cell line