Suppression of the Growth and Invasion of Human Head and Neck Squamous Cell Carcinomas via Regulating STAT3 Signaling and the miR-21/β-catenin Axis with HJC0152.
Suppression of the Growth and Invasion of Human Head and Neck Squamous Cell Carcinomas via Regulating STAT3 Signaling and the miR-21/β-catenin Axis with HJC0152.
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HJC0152 通过调节 STAT3 信号传导和 miR-21/β-catenin 轴抑制人头颈鳞状细胞癌的生长和侵袭
DOI：
10.1158/1535-7163.mct-16-0606
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发表时间：
2017-04
影响因子：
5.7
通讯作者：
Zhou X
中科院分区：
文献类型：
--
作者：
Wang Y;Wang S;Wu Y;Ren Y;Li Z;Yao X;Zhang C;Ye N;Jing C;Dong J;Zhang K;Sun S;Zhao M;Guo W;Qu X;Qiao Y;Chen H;Kong L;Jin R;Wang X;Zhang L;Zhou J;Shen Q;Zhou X
信号转导子和转录激活子3（STAT 3）参与人头颈部鳞状细胞癌（HNSCC）的生长和转移，是一个具有治疗潜力的靶点。在这项研究中，我们发现，HJC 0152，一个最近开发的抗癌药物和STAT 3信号抑制剂，表现出良好的抗肿瘤作用HNSCC在体外和体内通过灭活STAT 3和下游microRNA-21/β-catenin轴。HJC 0152处理有效地抑制HNSCC细胞增殖，将细胞周期阻滞在G 0/G1期，诱导凋亡，并减少SCC 25和CAL 27细胞系的细胞侵袭。此外，HJC 0152通过调节microRNA-21抑制磷酸化STAT 3在Tyr 705处的核转位，并降低VHL/β-catenin信号传导活性。VHL功能的丧失显著地损害了HJC 0152在两种细胞系中的抗肿瘤作用。在我们的SCC 25衍生的原位小鼠模型中，HJC 0152治疗显著地废除了体内STAT 3/β-catenin表达，这导致肿瘤生长和侵袭的整体降低。由于其良好的水溶性和口服生物利用度，HJC 0152有可能被转化为临床，成为HNSCC患者有前途的治疗策略。
Signal transducer and activator of transcription 3 (STAT3) is involved in the tumor growth and metastasis of human head and neck squamous cell carcinoma (HNSCC) and is therefore a target with therapeutic potential. In this study, we show that HJC0152, a recently developed anticancer agent and a STAT3 signaling inhibitor, exhibits promising antitumor effects against HNSCC both in vitro and in vivo via inactivating STAT3 and downstream microRNA-21/β-catenin axis. HJC0152 treatment efficiently suppressed HNSCC cell proliferation, arrested the cell cycle at the G0/G1 phase, induced apoptosis, and reduced cell invasion in both SCC25 and CAL27 cell lines. Moreover, HJC0152 inhibited nuclear translocation of phosphorylated STAT3 at Tyr705 and decreased VHL/β-catenin signaling activity via regulation of microRNA-21. Loss-of-function of VHL remarkably compromised the antitumor effect of HJC0152 in both cell lines. In our SCC25-derived orthotopic mouse models, HJC0152 treatment significantly abrogated STAT3/β-catenin expression in vivo, which leading to a global decrease of tumor growth and invasion. With its favorable aqueous solubility and oral bioavailability, HJC0152 holds the potential to be translated into the clinic as a promising therapeutic strategy for patients with HNSCC.