| Summary: | 碩士 === 高雄醫學大學 === 藥學系碩士班 === 103 === Gastric cancer is a high prevalent and mortality carcinoma in Taiwan. Ursolic acid (UA) is a pentacyclic triterpenoid isolated from Catharanthus trichophyllus roots. It has been reported to process anti-inflammatory and anti-tumor properties. However, the potential role of UA in the mechanism of death of gastric cancer has not been evaluated. Endoplasmic reticulum (ER) stress-related chaperone proteins, GRP78, are overexpressed in gastric cancer tissues, and are important for tumor development and chemotherapy sensitivity. Recently, cancer-associated fibroblasts (CAFs) in cancer microenvironments have been implicated in tumor growth and metastasis of various cancers. GRP78 may link with promoting fibroblasts activation by up-regulation of &;#61537;-SMA expression during tumor development. In this study, UA may promote cancer cell apoptosis and enhance chemosensitivity with combination of 5-fluorouracil (5-FU) by elimination of GRP78 and induction of excessive ER stress in cancer cell. Also, UA inhibits the expression of GRP78, as well as the activation of fibroblasts. Moreover, UA regulates GRP78 in gastric cancer through the transcription factor HOXA9 and YY1. Besides, UA decreases the expression of MMPs to inhibit invasion, and inhibits gastric cancer migration of gastric cancer through PAK1. In conclusions, these results indicate that UA induces gastric cancer cell death and suppresses fibroblasts activation as well as gastric cancer cell migration. UA may be regarded as a promising agent in anti-gastric tumor therapy.
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