从3,29-二苯甲酰基栝楼仁二醇抑制胶原沉积与过度交联改善胃癌微环境的作用揭示祖国医学“从痰论治肿瘤”思想的科学内涵

肿瘤相关成纤维细胞合成与释放大量的胶原及胶原修饰酶，引起肿瘤组织中胶原的沉积与过度交联，为肿瘤的发生发展营造了良好环境。抑制该病理过程可铲除肿瘤细胞赖以生存演进的适宜土壤，收釜底抽薪之效。申请人前期在祖国医学“从痰论治肿瘤”思想的指导下发现化痰中药瓜蒌中的3,29-二苯甲酰基栝楼仁二醇可有效抑制胃癌相关成纤维细胞对I型、VI型胶原及赖氨酸羟化酶2的表达。本项目将综合使用力学、超声医学、病理学、细胞生物学、分子生物学、表观遗传学的技术手段，研究该药能否抑制胃癌组织中胶原的沉积与过度交联，改善胃癌微环境，遏制胃癌的生长转移；并深入探究该药抑制I型、VI型胶原及赖氨酸羟化酶2表达的机制。若顺利实施，不仅可以发现新的药物用于肿瘤治疗，更可从中揭示祖国医学“从痰论治肿瘤”思想的深刻科学内涵，在中西医结合的过程中为形成祖国统一的新医学、新药学做出贡献。

Tumor-associated fibroblasts cause the deposition and over-crosslinking of collagen in tumor tissues by synthesizing and releasing a large amount of collagen and collagen modifying enzymes, which creates good physical and chemical environment for the initiation and progression of tumors. Inhibition of this pathological activity can eliminate the suitable soil on which tumor cells depend for survival and evolution. The applicant has examined the pathological activity under the guidance of the thought of "treating tumor from phlegm" in traditional Chinese medicine, and found that the 3,29-dibenzoyl-trichosanthes can effectively inhibit the expression of type I and type VI collagen and lysine hydroxylase-2 in gastric cancer-associated fibroblasts. In this project, three-dimensional co culture model and orthotopic tumor model of nude mice will be used to study whether 3,29-dibenzoyl-trichosanthinol can inhibit the deposition and over crosslinking of collagen in gastric cancer tissue, improve the microenvironment, and thus inhibit the growth and metastasis of gastric cancer. On this basis, the epigenetic mechanism of inhibition of collagen I and collagen VI and lysine hydroxylase 2 expression by the drug will be explored. The successful implementation of this project can not only find new drugs for tumor treatment, but also explain the scientific connotation of "treating tumor from phlegm" in traditional Chinese medicine, making contributions to exploration, enrichment and enhancement of traditional Chinese medicine.