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Clozapine Induces Senescence in Hepatocellular Carcinoma Cells
|Authors: ||Yi-Chia Lin|
|Contributors: ||NTOU:Institute of Bioscience and Biotechnology|
|Issue Date: ||2013-10-07T02:44:46Z
|Abstract: ||本實驗室先前已證明clozapine可抑制HepG2肝癌細胞株的增生，本論文進一步探討透過老化抑制肝癌細胞株HepG2和Huh-7增生之可能性。初步結果clozapine以time-dependent及dosage-dependent方式抑制HepG2和HuH7肝癌細胞株的增生，細胞週期停滯在G0/G1期，Annexin-V及PI染色發現clozapine並不會引起細胞凋亡，而SA-β-gal assay證實HepG2和Huh-7肝癌細胞株皆有老化的現象。西方墨點法偵測與老化相關之分子p21及 p27蛋白在HepG2細胞株有增加，未來擬利用RNAi knockdown去弱化標的基因，確認clozapine是調控肝癌細胞株老化的分子機制。|
Our previous data showed that clozapine could inhibit cell proliferation of HepG2 cells. Here, we further explore whether clozapine has the inhibitory effect on cell proliferation of hepatoma cell lines HepG2 and Huh-7 by senescence. Preliminary results showed that clozapine inhibited cell proliferation of HepG2 and Huh-7 cancer cells in both time-dependent and dosage-dependent manners by cell proliferation. Clozapine also led to cell cycle arrest at G0/G1 phase, but it did not induce apoptosis by Annexin-V/PI staining. Prologed clozapine treated cancer cells showed senescence phenotype including enlarged and flattened morphology and SA-β-gal activity. These related genes of senescence p53, p21 and p27 were upregulated in HepG2 cancer cells treated with 25 μM clozapine for 2, 4 and 6 days. We will knockdown the target gene using RNAi to elucidate the molecular mechanism of clozapine induced senescence in the future.
|Appears in Collections:||[生命科學暨生物科技學系] 博碩士論文|
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