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KMID : 1001020120100020090
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Korean Journal of Urological Oncology
2012 Volume.10 No. 2 p.90 ~ p.96
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An Anticancer Effect of Trichostatin A in Docetaxel-resistant Prostate Cancer Cells
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Lee Young-Ju
Yeon Jae-Seung
Kim Sung-Han
Lee Eun-Sik
Byun Seok-Soo
Lee Sang-Chul
Jeong Chang-Wook
Hong Sung-Kyu
Lee Sang-Eun
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Abstract
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Purpose: 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.
Results: Acute TSA administration (0-2?M 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 0.2?M 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.
Conclusions: PC3DR2 was established and our results suggest anti-tumor effect of TSA in inhibiting PC3DR2 through its proapoptotic effect.
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KEYWORD
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Prostate neoplasm, Trichostatin A, Histone deacetylase
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