STAT3小分子抑制剂HJC0152抑制人头颈部鳞癌细胞株侵袭迁移能力的研究

摘要

Objective:This study aims to explore the anticancer effects and potential mechanisms of HJC0152, a novel STAT3 inhibitor, on the invasion and migration capacities of human head and neck squamous cell carcinoma (HNSCC) cell lines in vitro. Methods:Cells were divided into two groups, the dimethyl sulfoxide (DMSO) group and the HJC0152 group in which HNSCC cell lines UM-1 and SCC-15 were treated with DMSO or HJC0152 for 24 h. The total expression levels of STAT3, p-STAT3 (Tyr705/Ser727), MMP-2/9, N/E-cadherin, TWIST1, and vimentin;and the cytoplasm and nuclear expression levels of STAT3 and p-STAT3 (Tyr705/Ser727) were detected by Western blot assay. Wound healing and Transwell assays were employed to detect the invasion and migration abilities of the UM-1 and SCC-15 cells. The expression and location of N/E-cadherin were visualized by immunofluorescence staining. Results:Western blot indicated that the total expression of p-STAT3 (Tyr705), MMP-2/9, N-cadherin, TWIST1, and vimentin were significantly declined and that E-cadherin was remarkably elevated in the HJC0152 group cells compared with that of the DMSO group, with no difference in STAT3 or p-STAT3 (Ser727). Cytoplasm and nuclear STAT3 (Tyr705) were also inhibited by HJC0152. Wound healing and Transwel assays indicated that tumor invasion and migration capacities were impressively attenuated in the HJC0152 group cells compared to that of the DMSO group. Conclusion:HJC0152 suppresses the phosphorylation of STAT3 at Tyr705 in the HNSCC cell lines, leading to impair transcription activity, deplete expression levels of target genes, and subsequently inhibit migration and invasion capabilities of HNSCC.%目的:探讨新型信号转导和转录活化因子3(signal transducer and activator of transcription,STAT3)抑制剂HJC0152对人头颈部鳞癌(head and neck squamous cell carcinoma,HNSCC)细胞株侵袭和迁移能力的影响及可能机制.方法:实验分为二甲基亚砜(DMSO)组和HJC0152组.Western blot检测细胞总蛋白中STAT3、p-STAT3 Tyr705/Ser727、MMP-2/9、N/E-cadherin、TWIST1和vi?mentin蛋白表达水平及核浆蛋白中的STAT3和p-STAT3 Tyr705/Ser727蛋白表达水平;划痕实验和Transwell实验检测细胞侵袭、迁移能力;免疫荧光实验观察N/E-cadherin蛋白的表达和亚细胞定位.结果:HJC0152组细胞总蛋白和核浆蛋白p-STAT3 Tyr705表达水平均受到显著抑制,而STAT3、p-STAT3 Ser727未见明显变化;总蛋白MMP-2/9、N-cadherin、TWIST1和vimentin表达水平降低,E-cadherin水平升高.HJC0152组细胞向划痕中央移动的距离明显短于DMSO组,通过Transwell小室聚碳酸酯膜的细胞较DMSO组也显著减少.结论:HJC0152可有效抑制头颈鳞癌细胞STAT3 Tyr705的磷酸化,阻碍其发挥转录因子的作用,抑制其下游基因表达,从而干预HNSCC侵袭和迁移能力.