| Summary: | 碩士 === 長庚科技大學 === 健康產業科技研究所 === 107 === Human hepatocellular carcinoma (HCC) is the second most common lethal malignancy in both sexes in Taiwan. Chemotherapy and surgical adjuvant therapy are not effective in patients with advanced HCC, due to tumor recurrence, primary tumor metastasis, and poor therapeutic response to chemotherapy and radiotherapy. Therefore, the development of therapeutic drugs with higher efficacy and milder side effects remains the key mission of liver cancer research. Hydroxygenkwanin (HGK) is a biologically active component extracted from Daphne genkwa. Currently, the understanding of HGK functions is limited, and there are no studies examining the anti-cancer activity of HGK in HCC. In this study, we treated liver cancer cells with different concentrations of HGK and found that the cell proliferation, migration, and invasion capabilities were significantly inhibited. A further examination of the mechanism revealed that besides epithelial mesenchymal transition (EMT)- related proteins, HGK also inhibited the expression of Class I histone deacetylases (HDAC) such as HDAC1, HDAC2, HDAC3, and HDAC8. This resulted in the induction of tumor suppressor proteins p21, thereby activating the downstream tumor suppressor pathways. Animal models revealed that HGK inhibited tumor growth in a synergistic manner with Sorafenib, suggesting that HGK has great potential as an adjuvant for HCC treatment.
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