Effection Of Alarelin On Subcutaneous Xenograft Growth Of Human Endometrial Carcinoma In Nude Mice

ObjectiveIn present research , we generated HEC-1B Hunman endometrial carcinoma subcutaneousxenograft models by injecting HEC-1B cells subcutaneously into the nude mouse , different doesof alarelin was administered alonely , and the effects on subcutaneous xenograft growth ,Caspase-3 and Livin expression.MethodsHuman endometrial carcinoma HEC-1B cells were cultured in vitro . To establish asubcutaneous xenograft animal model , human endometrial carcinoma HEC-1B cells wereinjected into the armpit on the right of the BALB/C nu/nu nude mouse subcutaneously .Removaling two nude mouse who with the biggest or the smallest subcutaneous xenograft , thenthirty-two nude mouse with subcutaneous xenograft were randomly divided into four groups:control group , the low dose alarelin group , the middle dose alarelin group , the high dosealarelin group . (0 , 20 , 40 , 80μg／kg , respectively) . During the period of treatment,thesystemic conditions of the mice were observed everyday , the size and volume of tumor weremeasured per five days , and growth curves of hunman endometrial carcinoma subcutaneousxenograft tumor in nude mice were drawed . Mouse were sacrificed four weeks after thetreatment,the tumor was removed and the volume of xenograft tumor were measured . Thechanges of xenograft morphology were observed by light microscopy with Hematoxylin-easinstaining staining , and the change of Caspase-3 and Livin expressions were estimated byimmunohistochemical technology .Results(1) The growth velocity of subcutaneous xenograft tumor were increase accord- ing to thehigh dose alarelin group , the middle dose alarelin group , the low dose alarelin group , controlgroup , and the difference was significant(P<0.05,respectively) .(2) After the treatment was finished , the tumor volume of each group was as follows :control group , 1764.90±245.80mm3 ; the low dose alarelin group , 1278.60±283.94 mm~3 ; the middle dose alarelin group , 1037.58±135.66 mm3 ; the high dose alarelin group , 942.59±131.36mm3 (P<0.05,respectively) . Different doses of alarelin prevented the growth tumorsin nude mice . At the end of the experiment , alarelin inhibited the tumor growth by 28.27%,41.21%and 46.23% in alarelin group of the low dose the middle dose and the high dose respecttively. The tumor grew slowly in each alarelin group compared with the control group , and thedifference was significant(P<0.05,respectively)．(3) The hematoxylin-easin staining results showed that control group filled with tumor cells ,and there were karyomegaly , karyokinesis , but alarelin group showed significant necrosis morphologychanges under a light microscope.(4) The immunohistochemical results showed that alarelin can increase the expression ofCaspase-3 , but decrease the expression of Livin . Adding to the doses of alarelin , the expressionof Caspase-3 increased gradually,and the difference was significant(P<0.05,respectively),but the expression of Livin decreased gradually(P<0.05) , and the difference between any twogroups of all the groups is significant(P<0.05) , except the difference between the middle dosegroup and high dose group(P>0.05) .ConclusiConclusion(1) Alarelin can significantly suppress tumor growth dose dependently .(2) It may be related to inhibite Livin expression and enhance Caspase-3 expression , tocause to apoptosis .