Primary Study Of Alarelin Inhibits Subcutaneous Xenotransplanted Tumor Formation Of Human Endometrial Carcinoma In Nude Mice And The Influence Of PCNA

Objective To study the anti-tumor effect and its mechanism of Alarelin at differentconcentration on human Endometrial carcinoma line HEC-1B implanted under the skin of nudemice in vivo.Methods Human endometrial carcinoma HEC-1-B cells were cultured in vitro.Nude micemode of transplanted human endometrial carcinoma was established by injecting HEC-1-B cellsinto subcutaneous of right lower limbs next groin,and after 3 days , twenty-four model nude micedivided into four groups randomly,which include the high dose Alarelin group、the middle doseAlarelin group、the low dose Alarelin group (the dose of Alarelin were 60ug／kg、30ug／kg、15ug／kg ) and blank control group(physiological saline). The status of growth inhabiting wasevaluated.The changes of xenograft morphology were observed by light microscopy with HEstaining.After treatment with Alarelin,the change of PCNA gene expressions were estimated byRT-PCR methods. Heart sections,liver sections and kidney sections were examined by HEstaining for assessment of toxicity.Results After 4 weeks of treatment(1)The blank control group in pathological observation showed cells became platy densely andfocal necrosis,nucleus became large and deeply stained, nucleus dissolution,nuclearfragmentation,chromation lumps also can be found.(2)the size of the xenografts of Alarelin groups were 1357.00±130mm~3in low dosegroup,1208.±98mm~3in middle dose group and 826 108mm~3in high dose grouprespectively,which were lower than the 1684 152 mm~3of control group(P<0.01), The tumorcontrol rate in low dose Alarelin group was 19.4%,while 25.3% in middle group and 51.0% inhigh dose group, The difference between the low dose group and the control group and thedifference between the high dose group and middle dose group are both significant(P <0.01).(3) The immunohisto-chemical showed that the expression level of PCNA decreased with theincreasing dose of Alarelin.(4) All the nude mice grew in a good condition.There were no abnormal changes in heartsections,liver sections and kidney sections examined under a light microscope and no toxicreactions during treatment.Conclusion Alarelin can inhibit the tumor growth of endometrial carcinoma of uterus,through the mechanism of down–regulating the expression of PCNA. Alarelin has no toxic reactions invivo treatment.