Effect Of Alarelin Acetate On Human Endometrial Carcinoma In Nude Mice Transplantation Tumor And Expression Of POT1

Objective:At present hormone analogue released by Gonadotropin can cure a variety of tumors.But it remains unclear of the specific mechanism of action and needs further study. To explore the inhibitory effects of Alarelin acetate on human endometrial carcinoma cell line HEC-1-B and study its molecular mechanisms. This study observes the effects of different doses of acetic Alarelin endometrial carcinoma xenograft tumor growth inhibition and affect of the expression of POT1, and the relationship between them.Methods:Human endometrial carcinoma HEC-1-B cells suspension cultured in vitro were inoculated 5-7-week-old female nude mice inoculated in the right hind leg near the groin subcutaneous. Endometrial cancer nude mice transplantation tumor model was established.To improve the accuracy, it needs to remove the maximum and minimum nude in the tumor volume after successful model. 32 tumor-burdened nude mice were randomly divided into four groups, 8 of each group. The first group was the control group. Group 2was Alarelin low dose group(20μg / kg). Group 3 was Alarelin dose group(40μg / kg).Group 4 was Alarelin high dose group(80μg / kg). Each group drug was formulated in different concentrations. Then they intervene by injecting each nude mouse 0.15 ml every time. The control group was injected with saline 0.15 m L once every day for 27 days. Nude mice were observed during the intervention in general(mental, diet, activity) and the injection site with or without ulceration. And the same experimenter measured diameter(a)and minor axis(b) of subcutaneous xenografts once with a vernier caliper every three days.It needs to be observed continuously 27 days. At the end of the experiment, thetransplantation tumors were completely removed, weighed and measured. Calculating the inhibition rate and detecting the expression of POT1 with the method of immunohistochemical.Results:First, Select BALB / C mice 32 and HEC-1-B of human endometrial cancer cell line.Subcutaneous injection of human endometrial carcinoma established xenografts in nude mice, tumor formation rate was 100. Transplanted tumors in each group comply with the characteristics of endometrial cancer before the intervention. They were viewed of nodular or round, encapsulated, hard and brittle.Second, the growth rate of the control group of Xenograft tumor was significantly higher than the experimental group. The growth rate of the low-dose group in nude mice was faster than the middle dose group. The growth rate of the dose group in nude mice was faster than the high-dose group. They showed that the control group was the fastest growth of the tumor.Third, After four weeks intervention, the volume of transplanted tumors are: the low-dose group, 0.570 ± 0.068cm3, middle dose group 0.451 ± 0.064cm3, high-dose group0.384 ± 0.036cm3. Compared with the control group, 0.725 ± 0.070cm3, there was a significant difference(P <0.05). Between the two groups, the difference was statistically significant(P <0.05). The inhibition rate of low-dose group was(21.38 ± 0.18)%, the inhibition rate of dose group was(37.76 ± 0.23)%, the inhibition rate of the high-dose group was(47.03 ± 0.26)%. Between the two groups, the difference was statistically significant(P <0.05).Fourth, after immunohistochemical staining, POT1 expression was brown or orange granules. Most of them were located in the cell cytoplasm(a few in the nucleus). With the increase of acetic acid, the stainings of Alarelin dose were deepening. Compared with the experimental control group, POT1 expression of the intervention group was significantlyincreased with different doses. Xenografts were intervented through the low medium high dose group of Alarelin, the expression of POT1 also increased. Differences were statistically significant(P <0.05) between the control group and the treatment group and between the treatment groups.Conclusions:First, Alarelin have direct inhibitory effect on nude mice which correlated with inhibition of the dose-Alarelin acetate in a certain range.Second, the mechanism of up-regulation of the POT1 may be through which Alarelin inhibited the activity of telomerase, shortened the length of the telomere, damaged the vigour of tumor cells, and then achieved the purpose of inhibiting tumors.