Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide  

作　　者：Mao-tao HUANG Zhi-xin CHEN Bing WEI Bo ZHANG Chun-hui WANG Ming-hui HUANG Rui LIU Cheng-weiTANG 

机构地区：[1]Departments of Gastroenterology,State Key Laboratoryof Biotherapy of Human Diseases, West China Hospital, Sichuan University, Chengdu 610041, China [2]Gastroenterology,State Key Laboratoryof Biotherapy of Human Diseases, West China Hospital, Sichuan University, Chengdu 610041, China [3]Surgery State Key Laboratoryof Biotherapy of Human Diseases, West China Hospital, Sichuan University, Chengdu 610041, China [4]Pathology State Key Laboratoryof Biotherapy of Human Diseases, West China Hospital, Sichuan University, Chengdu 610041, China [5]Division of Peptides Related with Human Diseases, State Key Laboratoryof Biotherapy of Human Diseases, West China Hospital, Sichuan University, Chengdu 610041, China

出　　处：《Acta Pharmacologica Sinica》2007年第11期1842-1850,共9页中国药理学报（英文版）

基　　金：a grant from National Natural Science Foundation of China(№ 30170418);the Key Program from the Department of Science and Technology of Sichuan Province,China(№ 02SG011-066)

摘　　要：Aim： To gain insight into the histopathological responses and molecular targets in the inhibition of growth of human gastric cancer treated with celecoxib （a cyclooxygenase [COX]-2 inhibitor） combined with octreotide. Methods： Seventy five patients with gastric cancer undergoing curative gastrectomy or extended resection were randomly divided into 3 groups. The apoptosis of tumor cells was measured by terminal deoxynucleotide transferase-mediated dUTP nick endlabeling （TUNEL） assay. Gastric cancer microvessel density （MVD） and the expression of COX-2 were evaluated by immunohistochemical staining. The expression of somatostatin receptor （SSTR）-2 was detected with the biomolecular interaction analysis system. The transcription of non-steroidal anti-inflammatory drugactivated gene （NAG）- 1 was measured by RT-PCR. Results： Compared with the control and celecoxib groups, more necrosis in the combination group was observed. The apoptotic rate in the combination group （7.06%±0.67%） was significantly higher than that in the control group （6.23%± 1.29%, P〈0.05）. The MVD decreased considerably in the combination group. The upregulation of NAG- 1 was displayed both in the celecoxib and combination groups. The positive rate of SSTR-2 in gastric cancers treated with celecoxib （48%） was significantly higher than that of control group （12%） after surgery （P〈0.05）. Conclusion： Celecoxib combined with octreotide significantly promoted necrosis in gastric adenocarcinoma through the induction of apoptosis and the reduction of MVD. NAG- 1 and SSTR-2 might be the molecular targets for celecoxib or octreotide.Aim： To gain insight into the histopathological responses and molecular targets in the inhibition of growth of human gastric cancer treated with celecoxib （a cyclooxygenase [COX]-2 inhibitor） combined with octreotide. Methods： Seventy five patients with gastric cancer undergoing curative gastrectomy or extended resection were randomly divided into 3 groups. The apoptosis of tumor cells was measured by terminal deoxynucleotide transferase-mediated dUTP nick endlabeling （TUNEL） assay. Gastric cancer microvessel density （MVD） and the expression of COX-2 were evaluated by immunohistochemical staining. The expression of somatostatin receptor （SSTR）-2 was detected with the biomolecular interaction analysis system. The transcription of non-steroidal anti-inflammatory drugactivated gene （NAG）- 1 was measured by RT-PCR. Results： Compared with the control and celecoxib groups, more necrosis in the combination group was observed. The apoptotic rate in the combination group （7.06%±0.67%） was significantly higher than that in the control group （6.23%± 1.29%, P〈0.05）. The MVD decreased considerably in the combination group. The upregulation of NAG- 1 was displayed both in the celecoxib and combination groups. The positive rate of SSTR-2 in gastric cancers treated with celecoxib （48%） was significantly higher than that of control group （12%） after surgery （P〈0.05）. Conclusion： Celecoxib combined with octreotide significantly promoted necrosis in gastric adenocarcinoma through the induction of apoptosis and the reduction of MVD. NAG- 1 and SSTR-2 might be the molecular targets for celecoxib or octreotide.

关 键 词：gastric adenocarcinoma CELECOXIB OCTREOTIDE non-cytotoxic agent SURGERY 

分 类 号：R735.2[医药卫生—肿瘤]