Abstract：
Esophagus cancer (EC) is one of the most aggressive malignant digestive system tumors and has a high clinical incidence worldwide. Magnolol, a natural compound, has anticancer effects on many cancers, including esophageal carcinoma, but the underlying mechanism has not been fully elucidated. Here, we first find that magnolol inhibits the proliferation of esophageal carcinoma cells and enhances their autophagy activity in a dose- and time-dependent manner. This study demonstrates that magnolol increases the protein levels of LC3 II, accompanied by increased HACE1 protein levels in both esophageal carcinoma cells and xenograft tumors. HACE1-knockout (KO) cell lines are generated, and the ablation of HACE1 eliminates the anti-proliferative and autophagy-inducing effects of magnolol on esophageal carcinoma cells. Additionally, our results show that magnolol primarily promotes HACE1 expression at the transcriptional level. Therefore, this study shows that magnolol primarily exerts its antitumor effect by activating HACE1-OPTN axis-mediated autophagy. It can be considered a promising therapeutic drug for esophageal carcinoma.
摘要：
食管癌(EC)是消化系统恶性程度最高的恶性肿瘤之一,在全球范围内具有较高的临床发病率。厚朴酚,一种天然化合物,对许多癌症有抗癌作用，包括食管癌,但是潜在的机制尚未完全阐明。这里,我们首先发现厚朴酚抑制食管癌细胞的增殖，并以剂量和时间依赖性的方式增强其自噬活性。这项研究表明，厚朴酚增加LC3II的蛋白质水平，伴随着食管癌细胞和异种移植肿瘤中HACE1蛋白水平的增加。产生HACE1敲除（KO）细胞系，HACE1的消融消除了厚朴酚对食管癌细胞的抗增殖和自噬诱导作用。此外,我们的结果表明厚朴酚主要在转录水平上促进HACE1的表达。因此,本研究表明厚朴酚主要通过激活HACE1-OPTN轴介导的自噬发挥抗肿瘤作用。它可以被认为是一种有前途的食管癌治疗药物。
