DataSheet_1_PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression.docx

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients.
Chemical Compounds Studied in this ArticleRutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).

胃癌是全球范围内第三大癌症致死病因。传统中医药（Traditional Chinese Medicine, TCM）作为胃癌（gastric cancer, GC）的补充治疗手段在我国的应用日益广泛，在预防胃癌转移方面展现出独特优势。既往研究表明，加味健脾养正方（modified Jian-pi-yang-zheng, mJPYZ）可通过调控肿瘤相关巨噬细胞（tumor-associated macrophages, TAM）抑制胃癌进展。然而，目前尚不清楚加味健脾养正方是否能够影响胃癌细胞的代谢重编程。本研究结果显示，加味健脾养正方可有效减弱胃癌细胞的增殖、迁移与侵袭能力。同时，加味健脾养正方可通过调控丙酮酸激酶M2（pyruvate kinase M2, PKM2）的表达及其核转位，在体内外降低胃癌细胞的有氧糖酵解水平。过表达PKM2可逆转加味健脾养正方对胃癌细胞迁移及上皮间质转化（epithelial to mesenchymal transition, EMT）的抑制作用。本研究结果证实，PKM2/缺氧诱导因子-1α（hypoxia-inducible factor-1α, HIF-1α）信号通路是加味健脾养正方调控胃癌细胞代谢的关键靶点。综上，本研究提示异常表达的PKM2是维持胃癌细胞恶性表型的必要条件。中药复方加味健脾养正方可通过依赖PKM2的方式降低胃癌细胞糖酵解水平，从而抑制其增殖与上皮间质转化。本研究拓展了我们对加味健脾养正方抗肿瘤作用机制的认知，并进一步表明加味健脾养正方有望成为胃癌患者潜在的抗肿瘤治疗药物。本文所研究的化学化合物：芦丁（Rutin, PubChem CID：5280805）；Lobetyolin（PubChem CID：53486204）；毛蕊异黄酮-7-葡萄糖苷（Calycosin-7-glucoside, PubChem CID：71571502）；芒柄花素（Formononetin, PubChem CID：5280378）；毛蕊异黄酮（Calycosin, PubChem CID：5280448）；芒柄花苷（Ononin, PubChem CID：442813）；对香豆酸（P-Coumaric Acid, PubChem CID：637542）。