Abstract：
BACKGROUND: Oral squamous cell carcinoma (OSCC) is associated with high recurrence and poor prognosis. Baicalin has multiple pharmacological effects, including anti-inflammatory and anti-proliferative activities. Here, we examine the effect of baicalein on OSCC metastasis and its potential mechanism of action.
METHODS: SCC-4 and CAL-27 cells were treated with different concentrations of baicalein. The proliferation of OSCC cells was evaluated by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. As for migration and metastasis, baicalein-treated OSCC cells were used for wound healing assay and Transwell assay. The levels of epithelial-mesenchymal transition-related proteins (E-cadherin, N-cadherin, vimentin) and extracellular regulated protein kinases (ERK)/ETS Transcription Factor ELK1 (ELK-1)/Snail signaling pathway-related proteins in baicalein-treated OSCC cells were evaluated by western blotting.
RESULTS: The rates of cell proliferation and migration, along with the metastatic potential, of baicalein-treated cells were significantly lower than those of the control (p < 0.05), and the effects were concentration-dependent. Furthermore, compared to the control, baicalein significantly decreased the levels of N-cadherin and vimentin in SCC-4 and CAL-27 cells, and increased the E-cadherin level (p < 0.05). Mechanistically, baicalein downregulated the levels of p-ERK1/2, phospho-ETS Transcription Factor ELK1 (p-ELK-1), and Snail (p < 0.05). Finally, the ERK/ELK-1/Snail pathway inhibitor (U0126) promoted the effect of baicalein in inhibiting the migration and invasion of OSCC cells (p < 0.05).
CONCLUSIONS: Baicalein abates the migration, invasion, and metastasis of OSCC cells through the ERK/ELK-1/Snail signaling pathway. This study provides a basis for the development of baicalein as a compound for the treatment of OSCC.
METHODS: SCC-4 and CAL-27 cells were treated with different concentrations of baicalein. The proliferation of OSCC cells was evaluated by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. As for migration and metastasis, baicalein-treated OSCC cells were used for wound healing assay and Transwell assay. The levels of epithelial-mesenchymal transition-related proteins (E-cadherin, N-cadherin, vimentin) and extracellular regulated protein kinases (ERK)/ETS Transcription Factor ELK1 (ELK-1)/Snail signaling pathway-related proteins in baicalein-treated OSCC cells were evaluated by western blotting.
RESULTS: The rates of cell proliferation and migration, along with the metastatic potential, of baicalein-treated cells were significantly lower than those of the control (p < 0.05), and the effects were concentration-dependent. Furthermore, compared to the control, baicalein significantly decreased the levels of N-cadherin and vimentin in SCC-4 and CAL-27 cells, and increased the E-cadherin level (p < 0.05). Mechanistically, baicalein downregulated the levels of p-ERK1/2, phospho-ETS Transcription Factor ELK1 (p-ELK-1), and Snail (p < 0.05). Finally, the ERK/ELK-1/Snail pathway inhibitor (U0126) promoted the effect of baicalein in inhibiting the migration and invasion of OSCC cells (p < 0.05).
CONCLUSIONS: Baicalein abates the migration, invasion, and metastasis of OSCC cells through the ERK/ELK-1/Snail signaling pathway. This study provides a basis for the development of baicalein as a compound for the treatment of OSCC.
摘要：
背景：口腔鳞状细胞癌（OSCC）与高复发和不良预后相关。黄芩苷具有多种药理作用,包括抗炎和抗增殖活性。这里,我们研究了黄芩素对OSCC转移的影响及其潜在的作用机制。
方法：用不同浓度的黄芩素处理SCC-4和CAL-27细胞。通过甲基噻唑基二苯基-溴化四唑（MTT）测定评估OSCC细胞的增殖。至于迁移和转移，将黄芩素处理的OSCC细胞用于伤口愈合测定和Transwell测定。上皮-间质转化相关蛋白(E-cadherin，N-钙黏着蛋白,波形蛋白）和细胞外调节蛋白激酶（ERK）/ETS转录因子ELK1（ELK-1）/Snail信号通路相关蛋白在黄芩素处理的OSCC细胞中通过蛋白质印迹进行评估。
结果：细胞增殖和迁移的速率，连同转移潜力，黄芩素处理的细胞显着低于对照组（p<0.05），效果是浓度依赖性的。此外，与对照相比，黄芩素显着降低SCC-4和CAL-27细胞中N-钙黏着蛋白和波形蛋白的水平，并增加E-cadherin水平（p<0.05）。机械上,黄芩素下调p-ERK1/2，磷酸-ETS转录因子ELK1（p-ELK-1）的水平，和蜗牛(p<0.05)。最后,ERK/ELK-1/Snail通路抑制剂(U0126)可促进黄芩素抑制OSCC细胞迁移和侵袭的作用(p<0.05)。
结论：黄芩素减轻迁移，入侵,OSCC细胞通过ERK/ELK-1/Snail信号通路转移。本研究为开发黄芩素作为治疗OSCC的化合物提供了依据。
方法：用不同浓度的黄芩素处理SCC-4和CAL-27细胞。通过甲基噻唑基二苯基-溴化四唑（MTT）测定评估OSCC细胞的增殖。至于迁移和转移，将黄芩素处理的OSCC细胞用于伤口愈合测定和Transwell测定。上皮-间质转化相关蛋白(E-cadherin，N-钙黏着蛋白,波形蛋白）和细胞外调节蛋白激酶（ERK）/ETS转录因子ELK1（ELK-1）/Snail信号通路相关蛋白在黄芩素处理的OSCC细胞中通过蛋白质印迹进行评估。
结果：细胞增殖和迁移的速率，连同转移潜力，黄芩素处理的细胞显着低于对照组（p<0.05），效果是浓度依赖性的。此外，与对照相比，黄芩素显着降低SCC-4和CAL-27细胞中N-钙黏着蛋白和波形蛋白的水平，并增加E-cadherin水平（p<0.05）。机械上,黄芩素下调p-ERK1/2，磷酸-ETS转录因子ELK1（p-ELK-1）的水平，和蜗牛(p<0.05)。最后,ERK/ELK-1/Snail通路抑制剂(U0126)可促进黄芩素抑制OSCC细胞迁移和侵袭的作用(p<0.05)。
结论：黄芩素减轻迁移，入侵,OSCC细胞通过ERK/ELK-1/Snail信号通路转移。本研究为开发黄芩素作为治疗OSCC的化合物提供了依据。
