Influence Of Alarelin On Subcutaneous Xenotransplanted Growth Of Human Endometrial Carcinoma In Nude Mice And The Expression Of PinX1

ObjectiveGonadotropin releasing hormones Analog have been used in clinical treatment of various tumor,but its mechanism still need to be further studied.In the present research,By observing inhibition of Alarelin on subcutaneous transplantation tumor growth of human endometrial carcinoma in nude mice and the expression of PinXl as well as the relationship between the two, to explore the possible mechanism of action of gonadotropin-releasing hormone analogue on endometrial cancer by the pathway of telomerase promoting tumor.MethodsHuman Endometrium Cancinoma HEC-1B cells were cultured in vitro, then subcutaneous transplantation tumor animal models of human endometrium carcinoma in nude mice were established. the experimental female nude mice of successful tumor-burdened building were randomly divided into four groups. They were normal saline control group, lower dose treatment groups, mild moderate dose treatment groups, high dose treatment group. Treatment groups were given different doses of Alarelin respectively were20ug/kg,40ug/kg,80ug/kg. With the mode of intramuscular injection, each nude mice was treated once per day for four consecutive weeks, explore the inhibition punction of Alarelin to subcutaneous transplantation tumor. By observing systemic condition of nude mice every day, measuring the volume of transplanted tumors in nude mice regularly during the period of treatment, we can draw the growth curve of Subcutaneous transplantation tumor and explore the inhibition punction of Alarelin to growth of tumor in nude mice。 When the experiment was finished, We execute the mice, remove subcutaneous transplantation tumor compeletely, weigh tumor, calculate the inhibition rate, observed the pathological changes of tumor cells under light microscopy; detect expression of PinXl protein in tumor tissues by immunohistochemical technology.Results1) During the early period of the tumor growth and drug treatment, nude mice grew well, their activity is normal.With the increase of tumor in nude mice, the experimental female nude mice becomed emaciated.Their spirit、appetite and activity were decreased.It was the most obviouse in high dose treatment group during the late experiment especially。(2) After4weeks intervention, the volume of the transplanted tumor respectively were1367.3±111.56mm3(low dose group),1123±117.4(mild moderate dose group),982±97.1mm3(high dose group),compare with the control group(1622.8±154.4mm3), and the differences are significant (P<0.01), the tumor control rate the treatment groups respectively were15.72%(low dose group),30.76%(mild miderate dose group),39.46%(high dose group).The difference betwen the low dose group and the middle dose group、 the difference betwen the low dose group and the control group and the difference betwen the low dose group and the high dose group are significant (P<0.01), different between the middle dose group and the high dose group isn’t significant(p=0.056)。(3) It was showed that control group filled with tumor cells in the ligh microscope, tumor cells are labour-intensive and lamellar disribution, Nucleoplasm radio imblance,nucleus karyolysis, karyorrhexis,chromatin into bass,the interstitial tissue reduce and cells proliferate activily. there were obviously xenotype and karyomegaly, anachromasis, karyokinesis. But alarelin group showed significant necrosis morphology changes under a light microscope:sparse arrangement of tumor cell and less cell atypia,visible large necrosis area without structure,some cells pyknosis, cracking, cell apoptosis and necrosis.no significant difference between Alarelin groups.(4) The immunohistochemical results showed that alarelin Can increase the expression of PinXl. Adding to the doses of alarelin, the expression of PinXl increased gradually(P<0.05). The difference between any two groups of all the groups is significant(P<0.05), except the difference between the middle dose group and high dose group(P>0.05).Conclusion(1)Alarelin has a direct inhibition to nude mouse transplantation tumor, and the inhibition has better dose-dependent within a certain range.(2) Alarelin can cause obvious changes of morpology of transplantation tumor.(3)The inhibitional effect of alarelin on subcutaneous transplantation tumor of huaman endometrial carcinoma in nude mice inhibitory be related to enhance PinXl expression, to inhibite cell proliferation and achieve the purpose of antitumor.