Ethyl ferulate is a phenylpropanoid compound isolated from the medicinal herb Ferula. Although ethyl ferulate has anti-inflammatory, antioxidant, and neuroprotective activities with potential use in the nutraceutical and pharmaceutical industry, its anticancer effects and underlying molecular mechanisms against esophageal squamous cell carcinoma (ESCC) have not been investigated. This study investigates the anticancer activity and molecular mechanism of ethyl ferulate in ESCC. MTT, focus formation, soft agar, and cell cycle analysis were used to determine the effect of ethyl ferulate on cell proliferation and cell cycle. Potential candidate proteins were screened and verified via Western blotting, in vitro kinase assay, and in vitro pull-down assay. Mammalian target of rapamycin (mTOR) knockdown cell lines were established by lentiviral infection with shmTOR. The effect of ethyl ferulate on tumor growth was assessed using ESCC patient-derived xenograft models. Ethyl ferulate significantly inhibited cell growth and induced G1 phase cell cycle arrest in ESCC cells. Ethyl ferulate reduced the activity of mTOR in vitro. The inhibition of ESCC cell growth by ethyl ferulate is dependent on mTOR expression. In addition, ethyl ferulate strongly reduced ESCC patient-derived xenograft tumor growth in an in vivo mouse model. Ethyl ferulate is an mTOR inhibitor that can suppress ESCC progression and may be a novel candidate compound for esophageal cancer chemoprevention.
中文翻译:
阿魏酸乙酯通过抑制 mTOR 信号通路抑制食管鳞状细胞癌肿瘤生长
阿魏酸乙酯是一种从药草中分离出来的苯丙烷类化合物阿鲁拉. 尽管阿魏酸乙酯具有抗炎、抗氧化和神经保护活性,在营养品和制药行业具有潜在用途,但其抗癌作用和针对食管鳞状细胞癌 (ESCC) 的潜在分子机制尚未得到研究。本研究探讨了阿魏酸乙酯在ESCC中的抗癌活性和分子机制。MTT、焦点形成、软琼脂和细胞周期分析用于确定阿魏酸乙酯对细胞增殖和细胞周期的影响。筛选和验证潜在的候选蛋白质通过蛋白质印迹法,体外激酶测定,和体外下拉试验。通过用 shmTOR 慢病毒感染建立哺乳动物雷帕霉素靶蛋白 (mTOR) 敲低细胞系。使用源自 ESCC 患者的异种移植模型评估阿魏酸乙酯对肿瘤生长的影响。Ethyl ferulate 显着抑制 ESCC 细胞的细胞生长并诱导 G1 期细胞周期停滞。阿魏酸乙酯降低 mTOR 的活性体外. 阿魏酸乙酯对 ESCC 细胞生长的抑制依赖于 mTOR 表达。此外,阿魏酸乙酯在体内鼠标模型。Ethyl ferulate 是一种 mTOR 抑制剂,可抑制 ESCC 进展,可能是食管癌化学预防的新型候选化合物。