The Pathway of Topotecan to Regulate HIF-1α in Human U87MG Glioma Cells
| Autor: | YANG,ZIH-CIAN, 楊子謙 |
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| Rok vydání: | 2016 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 104 Topotecan, an analogue of camptothecin as a topoisomerase I inhibitor, is a chemotherapeutic agent. Hypoxia-inducible factor-1 (HIF-1), a transcription factor, helps cancer cells adapt hypoxia environment and stimulate tumor growth. Human U87MG glioma cells belong to grade IV astrocytoma, which is the most common and most malignant primary brain cancer. In this study, U87MG glioma cells treated with topotecan increased sirtuin 1 (SIRT1) expression levels and decreased HIF-1α protein levels. HIF-1α regulates many downstream proteins involved in Warburg effect, such as hexokinase II (HK-II), lactate dehydrogenase A (LDHA), and pyruvate dehydrogenase kinase (PDK1). In our study, the expression levels of HK-II, LDHA, and PDK1 were decreased in U87MG cells when treated with topotecan. Also, topotecan decreased cell proliferation and TWIST protein expression levels in U87MG cells. In conclusion, these data suggested that topotecan may reduce the energy and fatty acid source and result in lower cancer cell proliferation through decreasing HIF-1α protein levels. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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