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

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

XUAN-FU XU,¹ CHUAN-GAO XIE,² XING-PENG WANG,³ JUN LIU,¹ YONG-CHUN YU,¹ HONG-LANG HU¹ and CHUAN-YONG GUO¹

¹Department of Gastroenterology, the Tenth Hospital, Tongji University, Shanghai, China
²Department of Gastroenterology, the Second Hospital, Zhejiang University, Hangzhou, China
³Department of Gastroenterology, the First Hospital, Jiaotong University, Shanghai, China

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.

keywords —— pancreatic neoplasm; cyclooxygenase-2; proliferation; celecoxib; NS398.

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Tohoku J. Exp. Med., 2008, 215, 149-157

Correspondence: Xuan-Fu Xu, Department of Gastroenterology, the Tenth People's Hospital, Tongji University, Shanghai 200072, China.

e-mail: shuanfusky@yahoo.com.cn