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Korean J Urol Oncol > Volume 10(2); 2012 > Article
The Korean Journal of Urological Oncology 2012;10(2): 90-96.
Docetaxel 내성 전립선암세포주에 대한 Trichostatin A의 항암효과
이영주, 연재승, 김성한, 이은식, 변석수1, 이상철1, 정창욱1, 홍성규1, 이상은1
서울대학교 의과대학 비뇨기과학교실, 1분당서울대학교병원 비뇨기과
An Anticancer Effect of Trichostatin A in Docetaxel-resistant Prostate Cancer Cells
Young Ju Lee , Jae Seung Yeon , Sung Han Kim , Eunsik Lee , Seok Soo Byun 1, Sang Chul Lee 1, Chang Wook Jeong 1, Sung Kyu Hong 1, Sang Eun Lee 1
Department of Urology, Seoul National University College of Medicine, Seoul, 1Seoul National University Bundang Hospital, Seongnam, Korea
Published online: August 30, 2012.
To determine anti-tumor effect of a histone deacetylase (HDAC) inhibitor, trichostatin A (TSA) in docetaxel- resistant human prostate cancer cells (PC3DR2).
Materials and Methods:
PC3DR2 was established from the PC3 prostate cancer cell line by continuous exposure to escalating concentrations of docetaxel. PC3 and PC3DR2 were exposed to escalating dose of TSA and tumor cell proliferation was examined by Cell Counting Kit-8 (CCK-8) assay. To evaluate the changes in cell cycle and apoptosis, flow cytometry was used and clonogenic assay was performed. Expression of cIAP1, PARP, caspase-3, and caspase-8 were analyzed by Western blot analysis.
Acute TSA administration (0-2ՌM for 24-72 hours) suppressed tumor cell proliferation in a time- and dose-dependent manner (p<0.05) in both prostate tumor cell lines. TSA with 0.2ՌM concentration induced G2/M phase cell cycle arrest in PC3 but not in PC3DR2 cell lines. A significant decrease in colony number was seen with the TSA treatment in the two cell lines. Western blot analysis revealed down-regulated cIAP1 and up-regulated PARP, caspase 8 and caspase 3 with the increasing concentrations of TSA in both cell lines.
PC3DR2 was established and our results suggest anti-tumor effect of TSA in inhibiting PC3DR2 through its proapoptotic effect. (Korean J Urol Oncol 2012;10:90-96)
Key Words: Prostate neoplasm; Trichostatin A; Histone deacetylase
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