Isoliquiritigenin, a flavonoid, eliminates gastric cancer stemness through inhibition of glucose-regulated protein 78

• Main Authors: Chao-Chun Lu, 盧昭均
• Other Authors: Yaw-Bin Huang
• Format: Others
• Language: zh-TW
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/81380478288788196792

碩士 === 高雄醫學大學 === 藥學系碩士班 === 105 === Gastric cancer (GC) is one of the leading causes of cancer-related death in the world. Accumulating evidence suggests that cancer stem cells (CSCs) are closely correlated to cancer recurrence and metastasis. However, the origination and mechanism that regulates CSCs remains unclear. Glucose regulated protein 78 (GRP78), an endoplasmic reticulum stress-related chaperone protein has been found to overexpress in gastric cancer, and may confer chemo-sensitivity. Isoliquiritigenin (ISL) is a flavonoid which derived from licorice, and is reported to inhibit GRP78 in breast cancer. The aims of this study are to investigate the connection between gastric CSC properties and GRP78, and whether ISL inhibits gastric cancer cells stemness through regulating GRP78. Initially, we confirm GRP78 was overexpressed in gastric cancer tissue by western blotting assay and immunohistochemistry. Subsequently, we found GRP78 was highly expressed in isolated tumor sphere of MKN45 cells. Therefore, we established GRP78 stable overexpressed MKN45 cells (GRP78+MKN45). GRP78+MKN45 cells exert cancer stemness properties. Moreover, 5-FU induces an increased expression of GRP78 in GC. ISL down-regulates the expression of GRP78 and suppresses stemness properties after chemotherapy. Thus, ISL may have the potential to serve as an adjuvant therapy for gastric cancer.