Honokiol induces apoptosis of lung squamous cell carcinoma by targeting FGF2-FGFR1 autocrine loop.
Honokiol induces apoptosis of lung squamous cell carcinoma by targeting FGF2-FGFR1 autocrine loop.
复制标题
和厚朴酚通过靶向 FGF2-FGFR1 自分泌环诱导肺鳞状细胞癌凋亡。
DOI：
10.1002/cam4.1846
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发表时间：
2018-12
期刊：
影响因子：
4
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Cen M;Yao Y;Cui L;Yang G;Lu G;Fang L;Bao Z;Zhou J
肺鳞状细胞癌(SCC)占肺癌病例的相当大比例，但目前仍缺乏有效的治疗方法。FGFR1扩增通常被认为是一个有前途的治疗靶点。和厚朴酚是一种化合物，已被证明对多种恶性肿瘤有效，其类似物已被报道针对FGFR1下游信号通路中的丝裂原激活蛋白激酶家族。这是一项探索性研究，旨在探讨和厚朴酚在肺鳞状细胞癌中的作用机制。我们发现和厚朴酚以时间和剂量依赖的方式诱导肺鳞状细胞癌细胞系的凋亡和细胞周期停滞。和厚朴酚还可抑制肺鳞状细胞癌细胞系的迁移。和厚朴酚对FGF2的表达和FGFR1的激活均有下调作用。药理抑制和siRNA抑制FGFR1诱导肺鳞状细胞癌细胞凋亡。我们的体内研究表明和厚朴酚可以抑制移植瘤的生长，这种作用与抑制FGF2-FGFR1信号通路有关。综上所述，和厚朴酚通过靶向FGF2-FGFR1自分泌环路诱导肺鳞状细胞癌细胞凋亡。
Lung squamous cell carcinoma (SCC) accounts for a considerable proportion of lung cancer cases, but there is still a lack of effective therapies. FGFR1 amplification is generally considered a promising therapeutic target. Honokiol is a chemical compound that has been proven to be effective against various malignancies and whose analog has been reported to target the mitogen‐activated protein kinase family, members of a downstream signaling pathway of FGFR1. This was an explorative study to determine the mechanism of honokiol in lung SCC. We found that honokiol induced apoptosis and cell cycle arrest in lung SCC cell lines in a time‐ and dose‐dependent manner. Honokiol also restricted cell migration in lung SCC cell lines. Moreover, the expression of FGF2 and the activation of FGFR1 were both downregulated by honokiol. Pharmacological inhibition and siRNA knockdown of FGFR1 induced apoptosis in lung SCC cells. Our in vivo study indicated that honokiol could suppress the growth of xenograft tumors, and this effect was associated with the inhibition of the FGF2‐FGFR1 signaling pathway. In conclusion, honokiol induced cell apoptosis in lung SCC by targeting the FGF2‐FGFR1 autocrine loop.
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影响因子：
4.9
作者：
Pernas S;Tolaney SM;Winer EP;Goel S
通讯作者：
Goel S
DOI：
10.1158/1078-0432.ccr-14-3357
发表时间：
2015-10-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Göke F;Franzen A;Hinz TK;Marek LA;Yoon P;Sharma R;Bode M;von Maessenhausen A;Lankat-Buttgereit B;Göke A;Golletz C;Kirsten R;Boehm D;Vogel W;Kleczko EK;Eagles JR;Hirsch FR;Van Bremen T;Bootz F;Schroeck A;Kim J;Tan AC;Jimeno A;Heasley LE;Perner S
通讯作者：
Perner S
影响因子：
3.4
作者：
Iwasaki, A;Kuwahara, M;Shirakusa, T
通讯作者：
Shirakusa, T
影响因子：
6.2
作者：
Lim, Sung Hee;Sun, Jong-Mu;Ahn, Myung-Ju
通讯作者：
Ahn, Myung-Ju
影响因子：
4.2
作者：
Chae, Jung-Il;Jeon, Young-Joo;Shim, Jung-Hyun
通讯作者：
Shim, Jung-Hyun