| Objective:Lung cancer is the leading cause of cancer-related death in the world.Non-small cell lung cancer（NSCLC）is the main type of lung cancer.Because there are little signs but more difficulty in diagnosis in the early stage,about 80%patients have reached the middle and advanced stage（stageⅢB-Ⅳ）of diagnosis and have lost the opportunity for surgery.Despite of the comprehensive multidisciplinary treatments,the overall survival rate of 5-year was only 10%to 16%.The formation and development of lung cancer was affected by multiple factors,links and pathways,and the difference between the tumor itself and the individual patient.Even in recent years,molecular targeted therapy and individualized therapy have not been satisfactory,but Chinese medicine has gradually shown its advantages in the treatment of lung cancer.Therefore,based on the theory-lung is related with kidney-in traditional Chinese medicine,it is of great significance to explore the mechanism of the effect of the internal environment of kidney deficiency on the occurrence and development of lung cancer.Thus,we could find out new specific indicators for the diagnosis of lung cancer,and establish a new treatment scheme to achieve individualized precise treatment.By establishing the model of kidney deficiency and lung cancer in ovariectomized mice,we observed the difference in growth rates of the transplanted Lewis lung cancer in male ovariectomized mice and normal mice,and the difference of the expression levels of sex hormones and the relative receptors in order to explore the mechanism of sex hormones on the occurrence and development of lung cancer.Methods:24 male C57BL/6 mice of 5662 days old were randomly divided into two groups,namely the castrated group and the control group.The case group was treated with abdominal resection of bilateral testes,and the control group was treated with bilateral testicular fat removal at the same site.After 2 weeks of recovery,we established the model of Lewis lung cancer by subcutaneous inoculation of tumor cell suspension.To observe the growth rates of transplanted tumors,the size in each mouse was measured every 5 days.3 weeks after the inoculation,all mice were weighed,taken serum and then taken off the neck to death.The weight of tumor and lung tissues,were measured respectively.Then,ELISA method was used to detect the serum levels of E2（Estrodiol,E2）and T（Testosterone,T）;IHC was used to detect the expression levels of AR（Androgen Receptor,AR）,ERα/β（Estrogen Receptorα/β,ERα/β）in the case and control group.Results:1.There were several changes in the mean weight of mice before and after castration.To compare the two groups of mice,the mean body weight of the mice in the control group was not statistically significant,P=0.496>0.05.However,before and after surgery,the mice in the castrated group had a weight loss,P=0.006<0.05,which was statistically different.2.The transplanted tumor volume of the ovariectomized mice increased rapidly in contrast with the control group,and the tumors were significantly different on the15th and 20th days after inoculation（P<0.05）.The tumor weight and lung weight of the transplanted tumors were higher than those of the control group,5.51±2.21/3.80±1.68,P=0.047<0.05;0.283±0.008/0.247±0.006,P=0.003<0.05.The lung tissues of two groups of mice were observed to calculate the lung metastasis rate.According to statistics,in the castrated group,the lung metastasis rate was 80%（8/10）,while in the control group,the lung metastasis rate was 58.33%（7/12）.At the same time,the number of pulmonary metastatic nodules was also significantly more than the control group,39.10±15.92/21.83±11.38,P=0.008<0.05.There are statistically significant differences in two groups.3.Compared with the control group,the serum levels of both E2 and T in castrated group decreased exponentially（154.68/287.39,2.15/5.32,both P<0.001）,the difference was statistically significant.And the ratio of E2/T increased,72.51±5.88./54.17±3.37,P<0.001,which was statistically different.4.The results of IHC showed that in the lung tissues of mice,AR,ERαand ERβwere highly expressed in two groups,and they were significantly higher in the castrated group,P<0.05.In the transplanted tumor tissues,there was no high expression of AR and ERαin the castrated group and control group,but in the castrated group,there were high expression of ERβ,P<0.05.As for the positive expression rates of AR,ERα,and ERβ,they were high in lung tissues of the castrated group,90%,80%,100%,which were statistically significant differences between the two groups（P<0.05）.In the tumor tissues,the positive rate of ERβexpression was statistically higher in the castrated group than that in the control group,P=0.04<0.05.However,the AR,ERαpositive expression rates in tumor tissues was not high,and there was no statistical difference between two groups.Conclusion:1.The internal environment of kidney deficiency caused by castration can disorder the sex hormone levels of C57BL/6 male mice,make the expression levels of sex hormone receptors abnormal,make the mice lose weight,but promote the growth of transplanted tumors,increase the numbers of lung metastatic nodules.2.It is the imbalance of sex hormones and abnormal expression of receptors that may affect the occurrence and development of lung cancer,which regulates the growth and metabolism of lung cancer cells,and promote the formation of lewis lung cancer transplanted tumor.3.The sex hormone receptor,especially ERβ,is expected to become a biomarker for lung cancer diagnosis and evaluation of prognosis. |
