Selective Inhibition of Cyclooxygenase-2 Suppresses the Growth of Pancreatic Cancer Cells in Vitro and in Vivo

• Published in: The Tohoku Journal of Experimental Medicine Vol. 215; no. 2; pp. 149 - 157
• Main Authors: Xu, Xuan-Fu, Xie, Chuan-Gao, Wang, Xing-Peng, Liu, Jun, Yu, Yong-Chun, Hu, Hong-Lang, Guo, Chuan-Yong
• Format: Journal Article
• Language: English
• Published: Japan Tohoku University Medical Press 2008
• Subjects: Administration, Oral; Aged; Animals; Celecoxib; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclooxygenase 2 - analysis; Cyclooxygenase 2 - immunology; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase 2 Inhibitors - therapeutic use; cyclooxygenase-2; Dose-Response Relationship, Drug; Female; Humans; Immunohistochemistry; In Vitro Techniques; Male; Mice; Mice, Nude; Middle Aged; Nitrobenzenes - administration & dosage; Nitrobenzenes - pharmacology; NS398; pancreatic neoplasm; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - prevention & control; Proliferating Cell Nuclear Antigen - metabolism; proliferation; Pyrazoles - administration & dosage; Pyrazoles - pharmacology; Radioligand Assay; Sulfonamides - administration & dosage; Sulfonamides - pharmacology; Tetrazolium Salts - metabolism; Thiazoles - metabolism; Time Factors; Tumor Burden - drug effects; Xenograft Model Antitumor Assays - methods
• ISSN: 0040-8727; 1349-3329
• DOI: 10.1620/tjem.215.149

Cyclooxygenase-2 (COX-2), a prostaglandin synthetase, is involved in development of certain tumors. We therefore analyzed COX-2 expression in pancreatic cancer tissues (53 samples) and Panc-1 human pancreatic cancer cells by immunohistochemistry, RT-PCR and western-blotting analyses. Also, immunohistochemistry of proliferating cell nuclear antigen (PCNA) was performed. We found expression of COX-2 was dramatically upregulated in 36 of 53 cases (67.9%) and the expression of COX-2 was associated with the diameter (> 3 cm) of the tumors (p < 0.05), but not with the age, gender, tumor location, differentiation, lymph-node metastases and TNM stage. The positivity rate of PCNA expression in the pancreatic cancer cells of the COX-2 positive group (32.88 ± 13.26%) was significantly higher than that in the COX-2 negative group (24.56 ± 11.51%) (p < 0.05). Then we investigated the effect of selective inhibitors of COX-2 (NS398 and celecoxib) on proliferation of Panc-1 cells by 3-(4,5 dimethyl-2-thiazolyl)-2.5-diphenyl-2H-tetrazolium bromide (MTT) assay. Either NS398 or celecoxib suppressed proliferation of Panc-1 cells dose-dependently in vitro. Furthermore, Panc-1 cells were implanted into nude mice, and celecoxib was administrated orally with feed. The volume of the tumor xenografted into nude mice was decreased by 51.6% in the celecoxib group (p < 0.01). In conclusion, the increased expression of COX-2 may be responsible for rapid proliferation of pancreatic cancer, and specific inhibition of COX-2 suppresses proliferation of Panc-1 cells in vitro and in nude mice. The selective inhibitor of COX-2 may be an effectual agent for pancreatic cancer chemoprevention.