Overcoming drug resistance in hormone- and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination.
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 >or=3-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.
Cengiz
Ercument
E
Division of Medical Oncology, Tulay Aktas Oncology Hospital, School of Medicine, Ege University, Izmir, Turkey.
Karaca
Burcak
B
Kucukzeybek
Yuksel
Y
Gorumlu
Gurbuz
G
Gul
Mustafa K
MK
Erten
Cigdem
C
Atmaca
Harika
H
Uzunoglu
Selim
S
Karabulut
Bulent
B
Sanli
Ulus A
UA
Uslu
Ruchan
R
D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000235:genetics; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006072:Gossypol / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000494:pharmacology*; D013997:Time Factors
D018076:DNA, Complementary; D043823:Taxoids; D000077143:Docetaxel; D006072:Gossypol