莱菔素抗食管癌的作用及分子机制研究

China was a high-risk areas for esophageal cancer, and the mortality rate of esophageal cancer ranked first in the world. The improvement of therapeutic effects and the prevention of recurrence are important strategies for oncotherapy. Our country is rich in natural Chinese herbal medicine resources, and natural products are an important source of anticancer drugs. Sulforaphene, a kind of isothiocyanates, derived from crucifer. Our initial findings showed sulforaphene can significantly suppresses viability, anchorage-independent growth and can induce apoptosis and G2-M arrest in esophageal cancer cells. Further we use supercomputer virtual screening technology to simulate the effect and found some related proteins which could bind with sulforaphene. However, the mechanism of action and molecular targets of esophageal cancer cell are unknown. This study will use protein kinase spectrum screening, gene expression chips, gene silencing and patient-derived xenograft (PDX) models et.al to illuminate the the mechanism of action and molecular targets of sulforaphene in esophageal cancer cell, which could support the experimental basis for clinical drug screening and provide an effective method for the treatment of esophageal cancer.

我国是食管癌高发地区，其死亡率一直位居世界首位。提高疗效及预防复发是肿瘤治疗的重要策略。我国有丰富的天然中药材资源，天然产物是抗肿瘤药物的重要来源，莱菔素是从十字花科植物中提取的异硫氰酸酯类物质。我们前期研究发现莱菔素能够有效抑制食管癌细胞的活性和锚定非依赖性生长，并能够明显诱导食管癌细胞凋亡和G2-M期阻滞，进一步我们利用超级计算机模拟初步筛选到了莱菔素的相关作用蛋白，但是莱菔素抑制食管癌细胞生长的作用机制及分子靶点并不清楚。本研究拟利用蛋白激酶谱筛查、基因表达芯片、基因沉默及人源性肿瘤组织异体移植模型等阐明莱菔素对食管癌细胞生长的影响、分子靶点及其抑制食管癌细胞生长的作用机制，从而为天然药物的临床筛选奠定实验基础，为食管癌的治疗提供新的思路。

我国是食管癌高发地区，其死亡率一直位居世界首位。提高疗效及预防复发是肿瘤治疗的重要策略。我国有丰富的天然中药材资源，天然产物是抗肿瘤药物的重要来源，莱菔素是从十字花科植物中提取的异硫氰酸酯类物质。本研究发现莱菔素能够有效抑制食管癌细胞的活性和锚定非依赖性生长，并能够明显诱导食管癌细胞凋亡和G2-M期阻滞，本研究利用蛋白质及磷酸化组学及人源性肿瘤组织异体移植模型等阐明莱菔素可通过作用于MSK2抑制食管癌细胞增殖，促进凋亡，从而为天然药物的临床筛选奠定实验基础，为食管癌的治疗提供新的思路。