Abstract：
BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN) is globally the sixth most common cancer. TGF-β1 is a key regulator of cell proliferation and differentiation, and it induces the epithelial-mesenchymal transition (EMT) by activating Smad2 signaling in SCCHN cells. Previous studies have revealed that oleuropein (OL) can inhibit the EMT alterations and migration of cancer cells. The aim of this study was to examine the involvement of TGF-β1 signaling pathway in SCCHN and the effect of OL on it.
METHODS: Through in vitro experiments at cellular level and in vivo evaluation in mouse xenograft tumor model, with morphological and Western blotting assays, we examined the effects of OL on TGF-β1-mediated signaling pathway in Tu686, CAL-27 and 686LN-M2 tumor cell lines.
RESULTS: We found that OL reversed the TGF-β1-induced EMT, and changed the morphology of cells and the expression levels of epithelial and interstitial markers. Wound-healing and transwell invasion assays indicated that OL reversed the TGF-β1-promoted cell migration and invasion dramatically. The effects of OL were also verified in xenograft tumor model of mice, and the findings were identical to the in vitro assays.
CONCLUSIONS: This study demonstrated that OL inhibits the growth and metastasis of SCCHN by interfering with the TGF-β1 signaling pathway, and the findings are beneficial for the development of prevention and treatment strategy of SCCHN. Due to the low toxicity and less side effects, OL may be of potential value in the inhibition of metastasis of SCCHN and improve survival.
METHODS: Through in vitro experiments at cellular level and in vivo evaluation in mouse xenograft tumor model, with morphological and Western blotting assays, we examined the effects of OL on TGF-β1-mediated signaling pathway in Tu686, CAL-27 and 686LN-M2 tumor cell lines.
RESULTS: We found that OL reversed the TGF-β1-induced EMT, and changed the morphology of cells and the expression levels of epithelial and interstitial markers. Wound-healing and transwell invasion assays indicated that OL reversed the TGF-β1-promoted cell migration and invasion dramatically. The effects of OL were also verified in xenograft tumor model of mice, and the findings were identical to the in vitro assays.
CONCLUSIONS: This study demonstrated that OL inhibits the growth and metastasis of SCCHN by interfering with the TGF-β1 signaling pathway, and the findings are beneficial for the development of prevention and treatment strategy of SCCHN. Due to the low toxicity and less side effects, OL may be of potential value in the inhibition of metastasis of SCCHN and improve survival.
摘要：
背景：头颈部鳞状细胞癌（SCCHN）是全球第六大最常见的癌症。TGF-β1是细胞增殖和分化的关键调节因子,它通过激活SCCHN细胞中的Smad2信号诱导上皮-间质转化（EMT）。先前的研究表明，橄榄苦苷（OL）可以抑制癌细胞的EMT改变和迁移。这项研究的目的是检查SCCHN中TGF-β1信号通路的参与以及OL对其的影响。
方法：通过细胞水平的体外实验和小鼠异种移植肿瘤模型的体内评估，通过形态学和蛋白质印迹分析，我们在Tu686、CAL-27和686LN-M2肿瘤细胞系中检测了OL对TGF-β1介导的信号通路的影响。
结果：我们发现OL逆转了TGF-β1诱导的EMT，改变细胞形态及上皮和间质标志物的表达水平。伤口愈合和transwell侵袭试验表明OL显著逆转了TGF-β1促进的细胞迁移和侵袭。在小鼠的异种移植瘤模型中也验证了OL的作用。结果与体外试验相同。
结论：本研究表明，OL通过干扰TGF-β1信号通路抑制SCCHN的生长和转移，研究结果有利于SCCHN防治策略的制定。由于毒性低，副作用少，OL可能在抑制SCCHN转移和改善生存率方面具有潜在价值。
方法：通过细胞水平的体外实验和小鼠异种移植肿瘤模型的体内评估，通过形态学和蛋白质印迹分析，我们在Tu686、CAL-27和686LN-M2肿瘤细胞系中检测了OL对TGF-β1介导的信号通路的影响。
结果：我们发现OL逆转了TGF-β1诱导的EMT，改变细胞形态及上皮和间质标志物的表达水平。伤口愈合和transwell侵袭试验表明OL显著逆转了TGF-β1促进的细胞迁移和侵袭。在小鼠的异种移植瘤模型中也验证了OL的作用。结果与体外试验相同。
结论：本研究表明，OL通过干扰TGF-β1信号通路抑制SCCHN的生长和转移，研究结果有利于SCCHN防治策略的制定。由于毒性低，副作用少，OL可能在抑制SCCHN转移和改善生存率方面具有潜在价值。
