Silibinin inhibits cell growth and induces apoptosis by caspase activation, down-regulating survivin and blocking EGFR-ERK activation in renal cell carcinoma
Silibinin inhibits cell growth and induces apoptosis by caspase activation, down-regulating survivin and blocking EGFR-ERK activation in renal cell carcinoma
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DOI：
10.1016/j.canlet.2008.06.033
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发表时间：
2008-12-08
期刊：
影响因子：
9.7
通讯作者：
Sun, Yi
中科院分区：
文献类型：
--
作者：
Li, Lei;Gao, Ye;Sun, Yi
水飞蓟宾在多种上皮癌模型中作为一种有效的抗癌和化学预防药物，已被报道通过有丝分裂信号通路抑制癌细胞生长。然而，它是否能抑制肾细胞癌的生长，其潜在的机制还不是很清楚。由于EGFR-MAPK和细胞凋亡通路在肾癌的生存中起着重要作用。在这里，我们首次评估了水飞蓟宾对肾癌生长的抑制作用，并研究了水飞蓟宾是否调节EGFR-MAPK和肿瘤细胞凋亡的级联信号。结果表明，水飞蓟宾通过抑制EGFR和ERK的激活，抑制Survivin的表达，上调P53的表达，触发caspase通路的级联，有效地抑制肾癌Caki-1细胞的增殖，诱导细胞凋亡。提示水飞蓟宾可能是肾癌治疗的候选化学预防药物之一。皇冠版权所有(C)2008由爱思唯尔爱尔兰有限公司出版。保留所有权利。
Silibinin as an effective anti-cancer and chemopreventive agent in various epithelial cancer models has been reported inhibition of cancer cell growth through mitogenic signaling pathways. However, whether it could inhibit renal cell carcinoma growth and what are the underlying mechanisms is still not well elucidated. Since EGFR-MAPK and apoptosis pathways play important roles in renal cell carcinoma survival. Here, for the first time we evaluated the inhibitory proliferation effects of silibinin in renal cell carcinoma growth and examined whether silibinin modulates EGFR-MAPK and tumor apoptosis cascades signals. Our results indicated that silibinin effectively inhibits the renal cancer carcinoma Caki-1 cell proliferation and induces apoptosis through inhibiting the activation of EGFR and ERK and the expression of survivin, up-regulating the expression of p53 and triggering the cascades of caspase pathways. Our results suggested silibinin might be as one of the candidate chemopreventive agents for renal cell carcinoma therapy. Crown copyright (C) 2008 Published by Elsevier Ireland Ltd. All rights reserved.