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    題名: Abnormal expression of JUNB gene in hepatocellular carcinoma
    作者: Chang, YS;Yeh, KT;Yang, MY;Liu, TC;Lin, SF;Chan, WL;Chang, JG
    貢獻者: 附設醫院醫研部;China Med Univ Hosp, Dept Mol Med, Taichung 404, Taiwan;Changhua Christian Hosp, Dept Pathol, Changhua, Taiwan;Kaohsiung Med Univ Hosp, Dept Internal Med, Div Hematol Oncol, Kaohsiung, Taiwan;Taipei Inst Pathol, Taipei, Taiwan
    日期: 2005
    上傳時間: 2010-09-24 15:01:25 (UTC+8)
    出版者: PROFESSOR D A SPANDIDOS
    摘要: This study delineates the antiproliferative activities and in vivo efficacy of YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole] in human hepatocellular carcinoma cells. YC-1 inhibited the growth of HA22T and Hep3B cells in a concentration-dependent manner without significant cytotoxicity. YC-1 induced G 1 phase arrest in the cell cycle, as detected by an increase in the proportion of cells in the G 1 phase using FAC-Scan flow cytometric analysis. It was further shown that cGMP, p42/p44 mitogen-activated protein kinase, or AKT kinase-mediated signaling pathways did not contribute to the YC-1-induced effect. Of note, YC-1 induced a dramatic increase in the expression of cyclin-dependent kinase (CDK)-inhibitory protein, p21(CIP1/WAP1), and a modest increase in p27(KIP1). The association of p21(CIP1/WAP1) with CDK2 was markedly increased in cells responsive to YC-1. YC-1 did not modify the expression of cyclin D1, cyclin E, CDK2, or CDK4. In a corollary in vivo study, YC-1 induced dose-dependent inhibition of tumor growth in mice inoculated with HA22T cells. Immunohistochemical analysis revealed an inverse relationship between the staining of p21(CIP1/WAF) and the staining of Ki-67, a cell proliferation marker. Based on the results reported herein, we suggest that YC-1 induces cell cycle arrest and inhibits tumor growth both in vitro and in vivo via the up-regulation of p21(CIP1/WAP1) expression in HA22T cells. Because of this, YC-1 is a potential antitumor agent worthy of further investigation.
    關聯: ONCOLOGY REPORTS 13(3):433-438
    顯示於類別:[台中附設醫院] 期刊論文

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