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 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.
General Surgery Department, Chang Gung Memorial Hospital, Kwei-Shan, Taoyuan, Taiwan, ROC.
Chun-Nan
CN
Yeh
Kun-Chun
KC
Chiang
Horng-Heng
HH
Juang
Jong-Hwei
JH
S Pang
Chung-Shan
CS
Yu
Kun-Ju
KJ
Lin
Ta-Sen
TS
Yeh
Yi-Yin
YY
Jan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000068579:Celecoxib; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018281:Cholangiocarcinoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016195:G2 Phase / Q000187:drug effects; D006498:Hepatectomy; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D049268:Positron-Emission Tomography; D011379:Prognosis; D016016:Proportional Hazards Models; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D016019:Survival Analysis
D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib