The Synthetic β-Nitrostyrene Derivative CYT-Rx20 Inhibits Esophageal Tumor Growth and Metastasis via PI3K/AKT and STAT3 Pathways.
The Synthetic β-Nitrostyrene Derivative CYT-Rx20 Inhibits Esophageal Tumor Growth and Metastasis via PI3K/AKT and STAT3 Pathways.
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DOI：
10.1371/journal.pone.0166453
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yuan SF
中科院分区：
文献类型：
--
作者：
Chiu WC;Lee YC;Su YH;Wang YY;Tsai CH;Hou YA;Wang CH;Huang YF;Huang CJ;Chou SH;Hsieh PW;Yuan SF
The β-nitrostyrene family have been implicated for anti-cancer property. However, the pharmacological role of β-nitrostyrene in esophageal cancer remain unclear. Here, a β-nitrostyrene derivative, CYT-Rx20, was synthesized and assessed for its anti-cancer activities and underlying mechanism in esophageal cancer. CYT-Rx20 induced cytotoxicity in esophageal cancer cells by promoting apoptosis through activation of caspase cascade and poly(ADP-ribose) polymerase (PARP) cleavage. Besides, CYT-Rx20 inhibited esophageal cancer cell migration and invasion by regulating the expression of epithelial to mesenchymal transition (EMT) markers. CYT-Rx20 decreased cell viability and migration through suppression of the PI3K/AKT and STAT3 pathways. Of note, the cytotoxicity and anti-migratory effect of CYT-Rx20 were enhanced by co-treatment with SC79 (AKT activator) or colivelin (STAT3 activator), suggesting the dependency of esophageal cancer cells on AKT and STAT3 for survival and migration, an oncogene addiction phenomenon. In xenograft tumor-bearing mice, CYT-Rx20 significantly reduced tumor growth of the implanted esophageal cancer cells accompanied by decreased Ki-67, phospho-AKT, and phospho-STAT3 expression. In orthotopic esophageal cancer mouse model, decreased tumor growth and lung metastasis with reduced Ki-67 and phospho-STAT3 expression were observed in mice treated with CYT-Rx20. Together, our results suggest that CYT-Rx20 is a potential β-nitrostyrene-based anticancer compound against the tumor growth and metastasis of esophageal cancer.
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影响因子：
4.6
作者：
Davies EJ;Dong M;Gutekunst M;Närhi K;van Zoggel HJ;Blom S;Nagaraj A;Metsalu T;Oswald E;Erkens-Schulze S;Delgado San Martin JA;Turkki R;Wedge SR;af Hällström TM;Schueler J;van Weerden WM;Verschuren EW;Barry ST;van der Kuip H;Hickman JA
通讯作者：
Hickman JA
影响因子：
3.3
作者：
Carter, KC;Finnon, YS;Waddell, R
通讯作者：
Waddell, R
影响因子：
3.7
作者：
Lennon FE;Mirzapoiazova T;Mambetsariev B;Poroyko VA;Salgia R;Moss J;Singleton PA
通讯作者：
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建立一种非侵入性半定量生物发光成像方法，用于监测原位食管癌小鼠模型。
影响因子：
3.7
作者：
Kuroda S;Kubota T;Aoyama K;Kikuchi S;Tazawa H;Nishizaki M;Kagawa S;Fujiwara T
通讯作者：
Fujiwara T
影响因子：
5.8
作者：
Kaap, S;Quentin, I;Steinfelder, HJ
通讯作者：
Steinfelder, HJ