Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro:: Possible involvement of inhibition of survival signal transduction pathways
Genistein, a tyrosine kinase inhibitor, enhanced radiosensitivity in human esophageal cancer cell lines in vitro:: Possible involvement of inhibition of survival signal transduction pathways
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DOI：
10.1016/s0360-3016(00)01560-1
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发表时间：
2001-05-01
影响因子：
7
通讯作者：
Mitsuhashi, N
中科院分区：
文献类型：
--
作者：
Akimoto, T;Nonaka, T;Mitsuhashi, N
目的：检查酪氨酸激酶抑制剂金雀异黄酮对放射敏感性的影响，特别关注“生存信号转导途径”。 方法和材料：使用两种人食管鳞状细胞癌细胞系 TE-1（p53，突变体）和 TE-2（p53，野生型）。通过克隆形成试验测定放射敏感性，并通过蛋白质印迹检查存活信号的激活，结果：金雀异黄素（30μM）通过抑制辐射诱导的存活信号、p42/p44细胞外信号调节激酶和AKT/PKB的激活，大大增强了这些细胞系的放射敏感性，在TE-2中观察到凋亡细胞百分比显着增加和聚[ADP-核糖]聚合酶裂解增加，但没有观察到在 TE-1 中，即使在金雀异黄素与辐射组合后也是如此。在p53相关蛋白表达变化方面，在TE-2中观察到Bax表达增加，而在TE-1中观察到Bcl-2表达减少，表明野生型p53细胞系中金雀异黄素诱导细胞死亡的主要模式与突变型p53不同。结论：本研究提示生存信号，包括p42/p44 ERK和AKT/PKB可能参与决定放射敏感性，和染料木黄酮将是一种有效的治疗剂，对辐射具有增强作用，(C) 2001 Elsevier Science Inc.
Purpose: The effect of genistein, a tyrosine kinase inhibitor, on radiosensitivity was examined, especially focusing on "survival signal transduction pathways."Methods and Materials: Two human esophageal squamous cell cancer cell lines, TE-1 (p53, mutant) and TE-2 (p53, wild), were used. Radiosensitivity was determined by clonogenic assay, and activation of survival signals was examined by Western blot,Results: Genistein (30 muM) greatly enhanced radiosensitivity in these cell lines by suppressing radiation-induced activation of survival signals, p42/p44 extracellular signal-regulated kinase and AKT/PKB, Significant increase in the percentage of apoptotic cells and increased poly[ADP-ribose] polymerase cleavage were observed in TE-2, but not in TE-1 even after combination of genistein with irradiation. In terms of changes in expression of p53-related proteins, increase in expression of Bax and decrease in that of Bcl-2 were observed in TE-2 but not in TE-1, suggesting that the main mode of cell death induced by genistein in a cell line with wild type p53 differed from that with mutant p53,Conclusions: This study suggested that survival signals, including p42/p44 ERK and AKT/PKB, may be involved in determining radiosensitivity, and genistein would be a potent therapeutic agent that has an enhancing effect on radiation, (C) 2001 Elsevier Science Inc.