Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma.
Cholangiocarcinoma (CCA), a lethal disease, affects many thousands worldwide yearly. Surgical resection provides the best chance for a cure; however, only one-third of CCA patients present with a resectable tumour at the time of diagnosis. Currently, no effective chemotherapy is available for advanc...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3724720?pdf=render |
| _version_ | 1819265567106793472 |
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| author | Chun-Nan Yeh Kun-Chun Chiang Horng-Heng Juang Jong-Hwei S Pang Chung-Shan Yu Kun-Ju Lin Ta-Sen Yeh Yi-Yin Jan |
| author_facet | Chun-Nan Yeh Kun-Chun Chiang Horng-Heng Juang Jong-Hwei S Pang Chung-Shan Yu Kun-Ju Lin Ta-Sen Yeh Yi-Yin Jan |
| author_sort | Chun-Nan Yeh |
| collection | DOAJ |
| description | Cholangiocarcinoma (CCA), a lethal disease, affects many thousands worldwide yearly. Surgical resection provides the best chance for a cure; however, only one-third of CCA patients present with a resectable tumour at the time of diagnosis. Currently, no effective chemotherapy is available for advanced CCA. Cyclooxygenase-2 (COX-2) is a potential oncogene expressing in human CCA tissues and represents a candidate target for treatment; however, COX-2 inhibitors increase the risk of negative cardiovascular events as application for chemoprevention aim. Here, we re-evaluated the effectiveness and safety of celecoxib, one widely used COX-2 inhibitor, in treating CCA. We demonstrated that celecoxib exhibited an anti-proliferative effect on CGCCA cells via cell cycle arrest at G2 phase and apoptosis induction. Treatment for 5 weeks high dose celecoxib (160 mg/kg) significantly repressed thioacetamide-induced CCA tumour growth in rats as monitored by animal positron emission tomography through apoptosis induction. No obviously observable side effects were noted during the therapeutic period. As retrospectively reviewing 78 intrahepatic mass-forming CCA patients, their survival was strongly and negatively associated with a positive resection margin and high COX-2 expression. Based on our result, we concluded that short-term high dose celecoxib may be a promising therapeutic regimen for CCA. Yet its clinical application still needs more studies to prove its safety. |
| first_indexed | 2024-12-23T20:47:26Z |
| format | Article |
| id | doaj.art-4adf58ebf2bd47fb8eb84f8a06d80c6c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T20:47:26Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-4adf58ebf2bd47fb8eb84f8a06d80c6c2022-12-21T17:31:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0187e6992810.1371/journal.pone.0069928Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma.Chun-Nan YehKun-Chun ChiangHorng-Heng JuangJong-Hwei S PangChung-Shan YuKun-Ju LinTa-Sen YehYi-Yin JanCholangiocarcinoma (CCA), a lethal disease, affects many thousands worldwide yearly. Surgical resection provides the best chance for a cure; however, only one-third of CCA patients present with a resectable tumour at the time of diagnosis. Currently, no effective chemotherapy is available for advanced CCA. Cyclooxygenase-2 (COX-2) is a potential oncogene expressing in human CCA tissues and represents a candidate target for treatment; however, COX-2 inhibitors increase the risk of negative cardiovascular events as application for chemoprevention aim. Here, we re-evaluated the effectiveness and safety of celecoxib, one widely used COX-2 inhibitor, in treating CCA. We demonstrated that celecoxib exhibited an anti-proliferative effect on CGCCA cells via cell cycle arrest at G2 phase and apoptosis induction. Treatment for 5 weeks high dose celecoxib (160 mg/kg) significantly repressed thioacetamide-induced CCA tumour growth in rats as monitored by animal positron emission tomography through apoptosis induction. No obviously observable side effects were noted during the therapeutic period. As retrospectively reviewing 78 intrahepatic mass-forming CCA patients, their survival was strongly and negatively associated with a positive resection margin and high COX-2 expression. Based on our result, we concluded that short-term high dose celecoxib may be a promising therapeutic regimen for CCA. Yet its clinical application still needs more studies to prove its safety.http://europepmc.org/articles/PMC3724720?pdf=render |
| spellingShingle | Chun-Nan Yeh Kun-Chun Chiang Horng-Heng Juang Jong-Hwei S Pang Chung-Shan Yu Kun-Ju Lin Ta-Sen Yeh Yi-Yin Jan Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma. PLoS ONE |
| title | Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma. |
| title_full | Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma. |
| title_fullStr | Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma. |
| title_full_unstemmed | Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma. |
| title_short | Reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma. |
| title_sort | reappraisal of the therapeutic role of celecoxib in cholangiocarcinoma |
| url | http://europepmc.org/articles/PMC3724720?pdf=render |
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