Reappraisal of the Therapeutic Role of Celecoxib in Cholangiocarcinoma

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

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

9 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
文章編號e69928
期刊PLoS ONE
8
發行號7
DOIs
出版狀態已出版 - 26 07 2013

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