Inhibitory Effect Of Antiangiogenic Dose Of Docetaxel And Celecoxib On Growth And Metastasis Of Gastric Cancer Orthotopicly Implanted In Nude Mice

Objective: To explore the effects of antiangiogenic dose of docetaxel and celecoxib on the growth and metastasis of gastric cancer in vivo and the mechanism of them inhibiting tumor. Methods: Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact tumor tissue obtained from repeated passage of SGC-7901 cell into the gastric wall of nude mice. Mice were randomly divided into 4 groups: control group(saline solution,3ml/d,orally administrated), docetaxel group (5mg/kg/d,continuely 4 days every week, ip), celecoxib group(10mg/kg/d,orally administrated), and combined treatment group both docetaxel(5mg/kg/d,continuely 4 days every week ip) and celecoxib(10mg/kg/d,orally administrated). Nine weeks after implantation, mice were sacrificed. Light and electron microscope were used to observe the structure of tumor; the metastasis of primary tumor to lymph node and liver were also studied; The weight was measured and the inhibition rate of tumor was obtained; immunohistochemical method were used to detect the micro vascular density(MVD) and the proliferating cell nuclear antigen(PCNA) and the PCNA index(PI) was calculated; The apoptosis of tumor cells measured by TUNEL method and the apoptosis index(AI) was calculated. Results: Compared with the control group, the orthotopically implanted tumors were significantly reduced in weight[(1.76±0.31) versus (0.89±0.20),(0.70±0.24) and (0.44±0.16)] in mice treated with docetaxel, celecoxib and combined treatment(P<0.01), Inhibitory Effect of Antiangiogenic Dose of Docetaxel and Celecoxib on Growth and Metastasis of Gastric Cancer Orthotopicly Implanted in Nude Mice Abstract with corresponding inhibition rates 49.4%,60.0% and 75.0%, respectively. The incidences of node metastases were 100%,60%,50%,30%; The incidences of liver metastases were 80%,50%,50%,20%. The node and liver metastases of combined group was significantly decreased than the control group(P<0.05). The MVD was also decreased significantly in the treated mice[(14.0±3.4) versus (7.0±3.2),(6.9±3.6) and (4.8±2.6)](P<0.01); The PI was also decreased significantly in the treated mice[(58.26±10.88) versus (36.54±11.48),(32.48±12.05) and (26.36±9.51)](P<0.01); The AI was increased significantly in treated mice[(2.56±1.57) versus (6.90±3.01),(7.34±2.93) and(11.10±3.52)] (P<0.01); And AI of the combined group was also significantly increased compared with the docetaxel and celecoxib groups(P<0.05). Conclusions: Both the docetaxel at the antiangiogenic dose and celecoxib can inhibit the growth and metastases of the gastric tumor by inhibit the angiogenesis, inhibit proliferating and induce apoptosis of the tumor cell. And it is more effective when combined used. And maybe combining of them would be used to treat the gastric cancer patients in the near future.