Study on the Effects of Cyclooxygenase-2 inhibitor NS-398 and CDK1/2 inhibitor NU6102 on the Relative Signaling Pathway in Human Lung Carcinoma Cell Line A549
碩士 === 國立成功大學 === 生命科學系碩博士班 === 95 === At present, cyclooxygenase exists in two distinct isoforms: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in human cells. COX-1 is constitutively expressed as a housekeeping enzyme in tissues whereas COX-2 is an inducible enzyme that is rapidly induced...
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ndltd-TW-095NCKU51050022015-12-11T04:04:29Z http://ndltd.ncl.edu.tw/handle/92373475701598347019 Study on the Effects of Cyclooxygenase-2 inhibitor NS-398 and CDK1/2 inhibitor NU6102 on the Relative Signaling Pathway in Human Lung Carcinoma Cell Line A549 在人類肺腫瘤細胞株A549細胞中NS-398和NU6102影響細胞內環氧合酵素相關路徑之研究 Hsin-Chung Huang 黃新中 碩士 國立成功大學 生命科學系碩博士班 95 At present, cyclooxygenase exists in two distinct isoforms: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in human cells. COX-1 is constitutively expressed as a housekeeping enzyme in tissues whereas COX-2 is an inducible enzyme that is rapidly induced by inflammatory and mitogenic stilmuli. It is known that prostaglandins (PGs) synthesized by COX-1 mediate normal physiological modulation while PGs synthesized by COX-2 are involved in many inflammatory diseases and cancer. During the progression of the cell cycle, the cell cycle is regulated by various cyclin-dependent kinases (CDKs). Many studies demonstrated that cancer cells often exhibit aberrant cell cycle regulation resulting in uncontrolled cell proliferation. Therefore, CDKs are another target for cancer therapies in addition to COX-2. It is worthy to notice that COX-2 was proved to stabilize survivin (an inhibitor of apoptosis) in cancer and survivin itself also associates with CDK1 and caspase-9 to form a complex that can modulate the progression of the mitotic phase and the inhibition of apoptosis. In our experiments, we investigated the signaling pathway involved in COX-2 inhibition by NS-398 in human lung carcinoma cell line A549. Moreover, we also examined whether NU6102 (a selective CDK1/2 inhibitor) has the potential to inhibit COX-2 expression. In this study, we found that COX-2 expression was significantly increased by starvation of A549 cells. Prostaglandins E2 receptor 2 (EP2) was found to be involved in COX-2 inhibition by NS-398. Interestingly, NU6102 was able to suppress starvation-induced COX-2 expression. Moreover, only ERK1/2 among three MAPKs was activated after A549 cells had been exposed to NS-398 or NU6102. PD098059, a specific inhibitor of MEK1, enhanced COX-2 inhibition by NS-398 or NU6102. In conclusion, we found that both NS-398 and NU6102 could inhibit COX-2 expression and the MEK/ERK signal pathway could be used to increase COX-2 expression in response to extracellular stimuli in A549 cells. Oi-Tong Mak 麥愛堂 2007 學位論文 ; thesis 74 en_US |
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碩士 === 國立成功大學 === 生命科學系碩博士班 === 95 === At present, cyclooxygenase exists in two distinct isoforms: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in human cells. COX-1 is constitutively expressed as a housekeeping enzyme in tissues whereas COX-2 is an inducible enzyme that is rapidly induced by inflammatory and mitogenic stilmuli. It is known that prostaglandins (PGs) synthesized by COX-1 mediate normal physiological modulation while PGs synthesized by COX-2 are involved in many inflammatory diseases and cancer. During the progression of the cell cycle, the cell cycle is regulated by various cyclin-dependent kinases (CDKs). Many studies demonstrated that cancer cells often exhibit aberrant cell cycle regulation resulting in uncontrolled cell proliferation. Therefore, CDKs are another target for cancer therapies in addition to COX-2. It is worthy to notice that COX-2 was proved to stabilize survivin (an inhibitor of apoptosis) in cancer and survivin itself also associates with CDK1 and caspase-9 to form a complex that can modulate the progression of the mitotic phase and the inhibition of apoptosis. In our experiments, we investigated the signaling pathway involved in COX-2 inhibition by NS-398 in human lung carcinoma cell line A549. Moreover, we also examined whether NU6102 (a selective CDK1/2 inhibitor) has the potential to inhibit COX-2 expression. In this study, we found that COX-2 expression was significantly increased by starvation of A549 cells. Prostaglandins E2 receptor 2 (EP2) was found to be involved in COX-2 inhibition by NS-398. Interestingly, NU6102 was able to suppress starvation-induced COX-2 expression. Moreover, only ERK1/2 among three MAPKs was activated after A549 cells had been exposed to NS-398 or NU6102. PD098059, a specific inhibitor of MEK1, enhanced COX-2 inhibition by NS-398 or NU6102. In conclusion, we found that both NS-398 and NU6102 could inhibit COX-2 expression and the MEK/ERK signal pathway could be used to increase COX-2 expression in response to extracellular stimuli in A549 cells.
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author2 |
Oi-Tong Mak |
author_facet |
Oi-Tong Mak Hsin-Chung Huang 黃新中 |
author |
Hsin-Chung Huang 黃新中 |
spellingShingle |
Hsin-Chung Huang 黃新中 Study on the Effects of Cyclooxygenase-2 inhibitor NS-398 and CDK1/2 inhibitor NU6102 on the Relative Signaling Pathway in Human Lung Carcinoma Cell Line A549 |
author_sort |
Hsin-Chung Huang |
title |
Study on the Effects of Cyclooxygenase-2 inhibitor NS-398 and CDK1/2 inhibitor NU6102 on the Relative Signaling Pathway in Human Lung Carcinoma Cell Line A549 |
title_short |
Study on the Effects of Cyclooxygenase-2 inhibitor NS-398 and CDK1/2 inhibitor NU6102 on the Relative Signaling Pathway in Human Lung Carcinoma Cell Line A549 |
title_full |
Study on the Effects of Cyclooxygenase-2 inhibitor NS-398 and CDK1/2 inhibitor NU6102 on the Relative Signaling Pathway in Human Lung Carcinoma Cell Line A549 |
title_fullStr |
Study on the Effects of Cyclooxygenase-2 inhibitor NS-398 and CDK1/2 inhibitor NU6102 on the Relative Signaling Pathway in Human Lung Carcinoma Cell Line A549 |
title_full_unstemmed |
Study on the Effects of Cyclooxygenase-2 inhibitor NS-398 and CDK1/2 inhibitor NU6102 on the Relative Signaling Pathway in Human Lung Carcinoma Cell Line A549 |
title_sort |
study on the effects of cyclooxygenase-2 inhibitor ns-398 and cdk1/2 inhibitor nu6102 on the relative signaling pathway in human lung carcinoma cell line a549 |
publishDate |
2007 |
url |
http://ndltd.ncl.edu.tw/handle/92373475701598347019 |
work_keys_str_mv |
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