Experimental Study Of The Effect Of NM-3 On The Angiogenesis In Nude Mice With Human Gastric Cancer

Objective: to explore the effect of a novel angiogenesis inhibitor NM-3and NM-3 in combination with Carboplatin on the growth of humangastric carcinoma SGC-7901 cell line in BALB/C nude mice and itsaction mechanism Of the effect of NM-3 on newborn microvascularangiogenesis surrounding human gastric cancer in nude mice.Motheds: The models with human gastric cancer SGC-7901 cell wereestablished by subcutaneous xenotransplantion.We fixed the pieces oftumor tissue under the dorsal skin of nude mice.These nude mice wererandomly divided into eight groups(10 nude mice in each group),i.e,saline control group,Carboplatin treatment group(5mg/kg),NM-3treatment group(includeing 3 subgroups) and NM-3 in combination withCarboplatin group(including3 subgroups).From the second day afterxenotransplantion,normal saline(20ml/kg),carboplatin(5mg/kg) andNM-3 at a dose of 10mg/kg,20mg/kg and 40mg/kg were administered i.p.respectively in the related groups three times a week for 6 weeks.At theend of the sixth week after treatment,the nude mice were sacrificed andthe intact tumor tissue was separated immediately, the volumn of tumor inmice was measured so as to calculate the tumor growth inhibitive rate,the level of apoptotic index(AI)of gastric cancer cell was assessed by normalstaining with HE and the microvascular density(MVD) in tumor tissuewas examined by immunohistochemical staining with anti-CD34monoclonal antibody.Results: 1,The volumn of subcutaneously implanted tumor in nude micein each group of NM-3 treatment alone and combinated treatment was915.46±39.66,871.26±38.84,812.27±32.59,692.40±58.43,548.32±66.02和382.13±43.52(mm~3) respectively, were significantly smallerthan that of saline control group(1609.55±41.32mm~3,p＜0.05).Thetmour inhibitive rate was 43.20±4.13％,45.87±4.62％,49.53±3.27％,56.98±5.34％,65.93±5.12％and 76.26±6.01％, in NM-3 dose-dependented manner, especially in groups with NM-3 therapy at dose40mg/kg.But the volumn of tumor in carboplatin treatment group did notdecrease sigificently compared with saline control group(1575.17±38.75mm~3 vs 1609.55±41.32mm~3,p＞0.05).The volumn of the tumordecreased and the inhibitive rate of tumor increased highly in combinatedgroups,compared with NM-3 treatment group alone at the same doseNM-3(p＜0.05),Compared with the saline control or Carboplatintreatment alone,the AI of gastric cancer cell was obviously increased andMVD in tumor tissue was significantly decreased in every mouse treated by NM-3(p＜0.05)and was related with NM-3 dose.But this differencedid not exist between NM-3 treatment group alone and combinedtreatment group at the same dose of NM-3,and between carboplatintreatment group and normal saline control group(p＞0.05) as wellConclusion A novel angiogenesis inhibitor NM-3 can inhibite thegrowth of the human no-differential gastric carcinoma SGC-7901 cellxenografted in nude mice by strongly decreaseing the angiogenesis intumor tissue and inducing apoptosis of human gastric cancercell.Forthermore,it can increase the inhibitive rate of the traditionalcellartoxial drug Carboplatin on gastric cancer in nude mice.