Qi Ye1, Li Su2, Dagui Chen2, Wenyi Zheng2, Ye Liu3. 1. School of Life Science, Fujian Agriculture and Forestry University, Fuzhou, China. 2. School of Pharmacy, Second Military Medical University, Shanghai, China. 3. Fuzhou General Hospital of Nanjing Military Region, Fujian Province, Fuzhou, China.
Abstract
BACKGROUND: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although chemotherapy is the primary means in colorectal cancer treatment, it is burdenerd by adverse drug effects. Drug-resistance is one of the most important challenges for chemotherapy and epithelial-mesenchymal transition (EMT) plays critical role in the development of drug resistance. AIMS: The aim of this study was to investigate the mechanisms underlying the effect of astragaloside IV (AS-IV) on miR-134 expression, EMT and chemotherapeutic sensitivity in CRC. METHODS: Cell proliferation, transfection assay, western blot, real-time PCR, cell migration and invasion assay and luciferase reporter assay were used to detect the effects of AS-IV on CRC. RESULTS: AS-IV significantly inhibited CRC cell migration and invasion by inducing miR-134 expression. Moreover, AS-IV and miR-134 increased the sensitivity of CRC tumors to oxaliplatin (OXA) chemotherapy. cAMP responsive element-binding protein 1 (CREB1), which was required for CRC cells migration, invasion and drug sensitivity, was significantly down-regulated by AS-IV. CONCLUSIONS: Our results indicated that AS-IV inhibited CRC EMT by inducing miR-134 expression which significantly down-regulated the CREB1 signaling pathway, and therefore increased the sensitivity to chemotherapy. Our findings provided new insight into the mechanisms of chemotherapy-resistant CRC, and may open new therapeutic options in the treatment of this devastating disease.
BACKGROUND:Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Although chemotherapy is the primary means in colorectal cancer treatment, it is burdenerd by adverse drug effects. Drug-resistance is one of the most important challenges for chemotherapy and epithelial-mesenchymal transition (EMT) plays critical role in the development of drug resistance. AIMS: The aim of this study was to investigate the mechanisms underlying the effect of astragaloside IV (AS-IV) on miR-134 expression, EMT and chemotherapeutic sensitivity in CRC. METHODS: Cell proliferation, transfection assay, western blot, real-time PCR, cell migration and invasion assay and luciferase reporter assay were used to detect the effects of AS-IV on CRC. RESULTS: AS-IV significantly inhibited CRC cell migration and invasion by inducing miR-134 expression. Moreover, AS-IV and miR-134 increased the sensitivity of CRC tumors to oxaliplatin (OXA) chemotherapy. cAMP responsive element-binding protein 1 (CREB1), which was required for CRC cells migration, invasion and drug sensitivity, was significantly down-regulated by AS-IV. CONCLUSIONS: Our results indicated that AS-IV inhibited CRC EMT by inducing miR-134 expression which significantly down-regulated the CREB1 signaling pathway, and therefore increased the sensitivity to chemotherapy. Our findings provided new insight into the mechanisms of chemotherapy-resistant CRC, and may open new therapeutic options in the treatment of this devastating disease.
Authors: Alexandru A Sabo; Maria Dudau; George L Constantin; Tudor C Pop; Christoph-M Geilfus; Alessio Naccarati; Mihnea P Dragomir Journal: Front Pharmacol Date: 2021-07-06 Impact factor: 5.810