| Summary: | 碩士 === 中臺科技大學 === 醫學檢驗生物技術系碩士班 === 104 === Sirtuin ( SIRT1) is a NAD+- dependent deacetylase protein, and a longevity-associated protein, which regulates hypoxia-inducible factor-1α（HIF-1α）. HIF-1α, a transcription factor, is a key regulator to hypoxia. In the present study, Irinotecan （CPT-11）, camptothecin（CPT） derivative, inhibits HIF-1α through SIRT1 activation in human U87MG glioma cells. We demonstrated that CPT-11 increased the expression of SIRT1 and decreased the expression of HIF-1α via deacetylation. Reduction of HIF-1α also decreased the expression of hexokinase-Ⅱ and Lactate dehydrogenase A to inhibit cell migration and reduce cell proliferation. On the other hand, CPT-11 increased the expression of cleaved Caspase 3 and cleaved PARP leading to cell apoptosis. These results were demonstrated that CPT-11 blocked HIF-1α expression through SIRT1 to regulate U87MG cells energy metabolism, cell survival, metastasis and apoptosis. In conclusion, these findings were suggested that CPT-11 may exert beneficial effects in the treatment of human glioma.
Key word: HIF-1α, SIRT1, Irinotecan（CPT-11）
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