The Drug Resistance Mechanism of Liver Cancer Stem Cells in Sorafenib Treatment

• Main Authors: LIAO, CHEN-CHUN, 廖振群
• Other Authors: CHAO, WEI-TING
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/jbqj4q

碩士 === 東海大學 === 生命科學系 === 106 === Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and comprises more than 90% of human liver cancers. Surgical resection is the best treatment for HCC, but only about 15% of patients are suitable for this treatment. To the unresectable or metastatic disease patients, chemotherapy is the only option for them. Sorafenib is the first line chemotherapy drug for advanced HCC. It is an oral multikinase inhibitor which can block tumor cell proliferation by targeting Raf kinase and angiogenesis by targeting vascular endothelial growth factor receptor (VEGFR). However, the prognosis of the patient is still poor because of the resistance and recurrence to chemotherapy, so it is importance to figure out the resistance mechanism of sorafenib treatment and develop new medical treatment especially for advanced HCC patients. There is increasing study support that cancer stem cells (CSCs) could be the reason for chemoresistance of sorafenib, but the resistance mechanism of CSCs is still unclear. In this study, the sorafenib resistance mechanism of CSCs in sorafenib treatment was examined in liver cancer cells. In vitro experiments, 8 μM sorafenib was used for the study. When the human liver cancer cells were treated with sorafenib for 48 hrs, the cancer stem cell markers, E-cadherin, SALL4 and CD90 are up-regulated. In vivo experiments, the subcutaneous injection of human liver cancer cells was performed in nu/nu mice, following with sorafenib treatment. After 21 days sorafenib treatment, we observe that PLC/PRF/5 and HepG2 cells with high E-cadherin expression were more resistance to sorafenib treatment. In the protein level, the cancer stem cell markers were not significant different after sorafenib treatment. However, sorafenib treatment can induce angiogenesis in tumors within two liver cancer cells. In conclusion, we suggest that sorafenib promotes the angiogenesis in high E-cadherin expression liver cancer cells and this pro-angiogenesis effect may highly related with CSCs.