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KMID : 1001020110090020062
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Journal of Urologic Oncology
2011 Volume.9 No. 2 p.62 ~ p.67
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An Anticancer Effect of Trichostatin A in Cis-platin-resistant BladderCancer Cells
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Park Ji-Hyun
Byun Seok-Soo
Lee Jeong-Eun
Oh Jong-Jin
Lee Sang-Chul
Hong Sung-Kyu
Yoon Cheol-Yong
Lee Eun-Sik
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 cis-platin resistant human bladder cancer cells(T24R2).
Materials and Methods: T24 bladder cancer cell line and T24R2 were exposed to escalating dose of TSA and tumor cell proliferation was examined by CCK-8 assay. To evaluate the changes in cell cycle and apoptosis, flow cytometry was used and clonogenic assay was performed. Expression of p21WAF1/CIP1, cIAP1, XIAP, Bcl-2, and Bax were analyzed by Western blot.
Results: Acute TSA administration(0.1-2?M for 24-72hours) suppressed tumor cell proliferation in a time- and dose-dependent manner(p＜0.05) in all two bladder tumor cell lines. TSA induced G1 phase cell cycle arrest in both bladder cell lines and higher-fraction of sub-G1(apoptotic portion) with 0.5?M in T24R2. A significant decrease in colony number was seen with the TSA treatment in the two cell lines. Western blot analysis revealed up-regulated p21 and bax, and down-regulated bcl-2, cIAP1 and xIAP with the increasing concentrations of TSA in both cell lines.
Conslusions: Our results suggest anti-tumor effect of TSA in inhibiting bladder cancer growths and its potential role as an agent for treating cisplatin-resistant bladder cancer.
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KEYWORD
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Urinary bladder neoplasms, Trichostatin A, Histone deacetylases
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