Inhibitory Effect Of Astragalus Polysaccharide On Growth In Transplanted Tumor Of Triple Negative Breast Cancer MDA-MB-231 In Nude Mice

Objective:To establish a human breast cancer xenograft model and observe the inhibitory effect of astragalus polysaccharides?APS?on the growth of human breast cancer MDA-MB-231 xenograft tumor in nude mice.And the effect of astragalus polysaccharide on the apoptosis of tumor cells was studied.Also,we discussed the role of astragalus polysaccharide in inhibiting the growth and inducing apoptosis of MDA-MB-231 in triple negative breast cancer and its possible molecular mechanism.Methods:A nude mouse xenograft model was established by injecting human breast cancer cell line MDA-MB-231 into the right axilla of BALB/c-nu nude mice.When the transplanted tumor of breast cancer nude mice reached 100 mm³,breast cancer xenografts were randomly divided into three groups,the model group?group M:0.9%saline?,the APS low dose group(group A:200 mg·kg^-1APS drug),and APS high dose group?group B:400 mg·kg^-11 APS drug?.There were 6 rats in each group.At the same time,6 normal nude mice were selected as normal group?N group:0.9%saline?.The drug was administered by gavage of 200?L daily for 21 days.The body weight of nude mice was observed every 2 days and the tumor size was measured during the administration.At the end of the experiment,the changes of body weight,tumor mass and tumor volume of APS low-and high-dose groups and model group were observed and compared.At the same time,the tumor inhibition rate and spleen index of nude mice in each group were calculated.Hematoxylin-eosin?HE?staining was used to observe the morphological changes of breast cancer tissues and liver and lung tissues of nude mice.TUNEL was used to detect apoptosis in breast cancer tissues in nude mice.And Western blot was used to detect the protein expression of apoptosis-related proteins including Bax,Bcl-2 and Caspase in breast cancer tissues.Results:?1?After treatment with APS,compared with the model group,the mass and volume of the APS low and high dose groups were significantly lower than that in the model group,and there was a significant difference between the groups?P<0.05?,and the tumor inhibition rates were 37.9%and 57.57%,respectively.?2?After APS drug intervention,compared with the model group,the spleen index in breast cancer nude mice of the APS low and the high-dose group were increased?P<0.05?;while the APS low and high dose group compared with the normal group showed no difference in spleen index?P>0.05?.?3?HE staining was used to detect the morphological changes of tissue cells.It showed that APS leads partial necrosis and apoptosis of tumor tissue in low and high dose groups.The morphology and structure of liver and lung tissue were normal,and there was no metastasis of liver and lung tissue in tumor cells.?4?TUNEL was used to detect apoptosis in breast cancer tissues in nude mice.The results showed that APS could induce the apoptosis in breast cancer cells.The apoptosis rates of tumor tissue in APS low and high dose group were significantly higher than that in model group?P<0.01?.?5?Western blot has been used to detect apoptosis-related proteins in breast cancer tissues.Compared with the model group,the expression of Bcl-2 protein in tumor tissue was decreased in the APS low and high dose groups?P<0.05?,and the expression of Bax,Caspase-9 and Caspase-7 in the tumor tissue was higher than that in the model group?P<0.05?.Conclusion:?1?Astragalus polysaccharide could significantly inhibit the growth of human breast cancer MDA-MB-231 xenograft tumor in vivo,and its mechanism may be related to the apoptosis of human breast cancer MDA-MB-231 cells induced by APS.?2?APS could change the expression of apoptosis-related proteins in nude mice with breast cancer in a dose-dependent manner.The expression of Bcl-2 was decreased,while the expression of Bax,caspase-7 and caspase-9 were increased significantly,and the ratio of Bax to Bcl-2 was increased significantly.?3?APS can participate in the mitochondrial apoptosis pathway of breast cancer cells by affecting the expression of apoptosis-related proteins Bcl-2,Bax,Caspase-9 and Caspase-7 in human breast cancer cell line MDA-MB-231.It promoted the apoptosis of breast cancer tissue and inhibited the growth of human breast cancer MDA-MB-231xenograft tumor in nude mice.