Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton and PI3K/Akt signaling pathways.
Silibinin suppresses bladder cancer through down-regulation of actin cytoskeleton and PI3K/Akt signaling pathways.
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DOI：
10.18632/oncotarget.20734
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发表时间：
2017-11-03
期刊：
影响因子：
--
通讯作者：
Yamamura S
中科院分区：
文献类型：
--
作者：
Imai-Sumida M;Chiyomaru T;Majid S;Saini S;Nip H;Dahiya R;Tanaka Y;Yamamura S
水飞蓟宾是水飞蓟素的主要活性成分，水飞蓟素是水飞蓟种子的提取物。水飞蓟宾已被证明在多种恶性肿瘤中具有显著的抗癌作用。然而，水飞蓟宾在膀胱癌中作用的分子机制尚未得到广泛研究。在本研究中，我们发现水飞蓟宾(10μM)显著抑制人膀胱癌T24和UM-UC-3细胞的增殖、迁移、侵袭和诱导细胞凋亡。水飞蓟宾下调这些癌细胞系的肌动蛋白细胞骨架和磷脂酰肌醇3-激酶(PI3K)/Akt信号通路。这些通路被发现在RAS级联中串扰。我们发现水飞蓟宾抑制了KRAS启动子上三甲基化组蛋白H3、赖氨酸4和乙酰化H3的水平。此外，水飞蓟宾针对的是长非编码RNA：HOTAIR和ZFAS1，这两个已知在各种癌症中扮演致癌因子的角色。本研究表明水飞蓟宾通过下调肌动蛋白细胞骨架和PI3K/Akt通路发挥抗癌作用，从而抑制膀胱癌的生长和发展。
Silibinin is the major active constituent of silymarin, an extract of milk thistle seeds. Silibinin has been shown to have significant anti-cancer effects in a variety of malignancies. However, the molecular mechanisms of silibinin action in bladder cancer have not been studied extensively. In the present study, we found that silibinin (10 μM) significantly suppressed proliferation, migration, invasion and induced apoptosis of T24 and UM-UC-3 human bladder cancer cells. Silibinin down-regulated the actin cytoskeleton and phosphatidylinositide 3-kinase (PI3K)/Akt signaling pathways in these cancer cell lines. These pathways were found to crosstalk through RAS cascades. We found that silibinin suppressed levels of trimethylated histone H3 lysine 4 and acetylated H3 at the KRAS promoter. Furthermore, silibinin targets long non-coding RNA: HOTAIR and ZFAS1, which are known to play roles as oncogenic factors in various cancers. This study shows that silibinin exerts anti-cancer effects through down-regulation of actin cytoskeleton and PI3K/Akt pathways and thus suppresses bladder cancer growth and progression.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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Singh PK
DOI：
10.1158/1078-0432.ccr-10-2290
发表时间：
2011-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Ramasamy K;Dwyer-Nield LD;Serkova NJ;Hasebroock KM;Tyagi A;Raina K;Singh RP;Malkinson AM;Agarwal R
通讯作者：
Agarwal R