Title: PT-262誘發細胞凋亡與抑制腫瘤形成的作用
Induction of apoptosis and tumorigenesis inhibition by PT-262
Authors: 李靜怡
Li, Jin- Yi
趙瑞益
Chao, Jui-I
生物科技學系
Keywords: 細胞凋亡;腫瘤形成;肺癌細胞;apoptosis;tumorigenesis;human lung cancer cells;PT-262
Issue Date: 2009
Abstract: 本論文為探討一種由6,7-dichloro-quinoline-5,8-dione所衍生的新合成化合物,稱為7-chloro-6-piperidin-1-yl-quinoline-5, 8-dione,簡稱PT-262,研究其抗癌的能力。PT-262具有誘發A549人類肺癌細胞產生細胞毒性及細胞凋亡的作用。處理PT-262後會促使細胞凋亡蛋白caspase 3被活化與其下游分子PARP蛋白的切割。同時,我們發現PT-262會降低抗細胞凋亡蛋白,包括survivin及XIAP的表達,相反地,處理PT-262之後,會誘發參與調控細胞凋亡的調控蛋白p38與H2AX的蛋白磷酸化活化量增加。有趣地,PT-262會增加具有抑制腫瘤功能E-cadherin蛋白表達,並且表現於A549肺癌細胞的細胞膜,然而PT-262並不影響E-cadherin基因的表達。再者,PT-262具有抑制先天免疫缺失的老鼠體內之異種移植人類肺癌腫瘤的形成能力。綜合以上結果,我們提供PT-262具有誘發人類肺癌細胞凋亡及抑制腫瘤形成的抗癌活性,並推測PT-262是一種有潛力的化合物,可提供作為開發未來肺癌的治療。
A new synthetic compound 7-chloro-6-piperidin-1-yl-quinoline-5, 8-dione (designed as PT-262) derived from 6, 7-dichloro-quinoline-5, 8-dione on its anticancer ability was investigated in this study. PT-262 induced cytotoxicity and apoptosis in A549 lung carcinoma cells. The activated caspase 3 and the cleaved form of PARP proteins were induced by treatment with PT-262. Meanwhile, we found that PT-262 reduced anti-apoptosis proteins expression including survivin and XIAP. In contrast, the phosphorylation of p38 and H2AX, the apoptotic-regulated proteins, were activated by PT-262. Interestingly, PT-262 increased a tumor suppressor protein E-cadherin expression, which located in the membrane of A549 lung cancer cells; however, the gene expression of E-cadherin was not altered by PT-262. Furthermore, PT-262 inhibited tumorigenesis of xenograft lung cancer cells in severe combined immunodeficiency (SCID) mice. Together, our findings provide that PT-262 exerts the anticancer activities on apoptosis induction and tumorigenesis inhibition in human lung cancer cells. We suggest that PT-262 is a novel and potential chemical for developing cancer therapy in lung cancer.
URI: http://140.113.39.130/cdrfb3/record/nctu/#GT079728527
http://hdl.handle.net/11536/45300
Appears in Collections:Thesis


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