Primary Study Of Alarelin Inhibits Subcutaneous Xenotransplanted Tumor Formation Of Human Endometrial Carcinoma In Nude Mice And The Expression Of Survivin Gene

Objective To study the anti-tumor effect and its mechanism of Alarelin at different concentration on human Endometrial carcinoma line HEC-1B implanted under the skin of nude mice in vivo.Methods Human endometrial carcinoma HEC-1B cells were cultured in vitro. The models of xenografted tumor were established by the transplantation of human endometrial carcinoma HEC-1B cell on nude mice,twenty-four nude mice with xenograft of endometrial carcinoma HEC-1B were divided randomly into four groups,namely, the control group,the low dose Alarelin group,the middle dose Alarelin group,the high dose Alarelin group. The nude mice of control group were treated by intramuscular injection of normal saline,The nude mice of Alarelin groups were treated by intramuscular injection of different concentrations of Alarelin(the dose of Alarelin were 15ug/kg,30ug/kg,and 60ug/kg respectively).The status of growth inhabiting was evaluated.The changes of xenograft morphology were observed by light microscopy with HE staining. After treatment with Alarelin, the change of survivin gene expressions were estimated by RT-PCR methods. Heart sections,liver sections and kidney sections were examined by HE staining for assessment of toxicity.Results After 6 weeks of treatment:(1) the size of the xenografts of Alarelin groups were 1106.0±116.9mm3,1162.8±145.4mm3 and 1341.6±145.2mm3 respectively,which were lower than the 1610.0±166.9 mm3 of control group(P＜0.01), The tumor control rate in low dose Alarelin group was 16.70%,while 27.76% in middle group and 31.30% in high dose group, The difference between the low dose group and the control group and the difference between the low dose group and middle dose group are both significant(P<0.01).The difference between the middle dose group and the high dose group is not significant(P=0.375); (2) Compared with control group, the expression of Survivin mRNA significantly decreased in experimental groups(P<0.05).The difference between any two group of all the groups is significant,except the difference between the middle dose group and high dose group.Alarelin down-regulated survivin gene expressions of Subcutaneous Xenotransplanted implanted tumors; (3) The xenograft of Alarelin group showed significant necrosis morphology changes under a light microscope; (4) All the nude mice grew in a good condition. There were no abnormal changes in heart sections, liver sections and kidney sections examined under a light microscope and no toxic reactions during treatment.Conclusion Alarelin could inhibit the Subcutaneous Xenotransplanted of human endometrial carcinoma in nude mice and its mechanism may be associated with Survivin gene lower-expressions. Alarelin has no toxic reactions in vivo treatment.