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Cis-platin 내성 방광암세포주에 대한 Trichostatin A의 항암효과 분석
박지현(Jihyun Park),변석수(Seok-Soo Byun),이정은(Jeong Eun Lee),오종진(Jong Jin Oh),이상철(Sang Chul Lee),홍성규(Sung Kyu Hong),윤철용(Cheol Yong Yoon),이은식(Eunsik Lee),이상은(Sang Eun Lee) 대한비뇨기종양학회 2011 대한비뇨기종양학회지 Vol.9 No.2
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 (0.1-2μM 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 0.5μM 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. Conclusions: 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.