The Effects Of ASP On Tumor Growth And Iron Metabolism In Tumor-Bearing Mice

BackgroundIncreasing evidence indicated that iron overload may contribute to tumor initiation,behavior and recurrence.Angelica sinensis polysaccharide(ASP)is the major bioactive component extracted from roots of angelica.Recently,studies have demonstrated that ASP has various biological functions,including immunomodulation,anti-tumor activity,and hematopoiesis.The results of our previous study showed that ASP could reduce the expression of hepcidin in human hepatocellular carcinoma HepG2 cells in vitro.It is worth noting that Hepcidin is an important factor in the regulation of iron content in the body.ObjectivesThe aim of this study is to explore the effects of ASP on tumor growth and iron metabolism in tumor bearing mice by animal experiment,immunohistochemistry,atomic absorption spectrophotometer and multifunctional automatic biochemical analyzer.Methods1.The effects of ASP on tumor growth in tumor bearing mice were studied by tumor-bearing mice.The mice breast cancer 4T1 cells and mouse liver cancer H22 cells were taken as objects.The control group(saline group),cyclophosphamide(CTX)group and ASP group were established respectively.2.The expression of Ki-67 in tumor tissues of mice was observed by immunohistochemistry(IHC).3.The changes of iron(liver,spleen and tumor tissue)in each group were detected by hematoxylin-eosin(HE)staining and atomic absorption spectrophotometer.4.The serum iron level in each group was detected by a multifunctional automatic biochemical analyzer.Results 1.Effects of ASP on tumor growth in tumor bearing miceThe animal experiment results demonstrated that,Compared with the control group,the tumors in CTX group and ASP group were light weight(P< 0.05)and small in size(P< 0.05)in 4T1 and H22tumor-bearing mice,respectively.Furthermore,Compared with the CTX group,the tumors in ASP group were heavy weight(P< 0.05)and large volume(P< 0.05)in 4T1 and H22tumor-bearing mice,respectively.IHC confirmed that tumors of the control group displayed much higher Ki-67 indices than tumours from the ASP group(P< 0.01)in 4T1 and H22 tumor-bearing mice,respectively.2.Effects of ASP on the tissue ironHE staining results revealed that,The liverand spleensections taken from the control group mice showed increased hemosiderin depositions compare to the blank group.However,the liver,spleen,and tumor sections taken from the ASP-treated mice showed decrease in the deposition of hemosiderin.Iron concentration in these organs were determined by atomic absorption spectrophotometer.The results showed that in 4T1 tumor-bearing mice the iron concentration of liver and spleen incontrol group mice increased 2.71,and 4.55-fold compared to the blank group,respectively(P< 0.001).And following treatment with ASP,the iron concentration in these organs were significantly reduced 38.53%,32.88% and 55.89% in comparison to the controlgroup,respectively(P< 0.001).And in H22 tumor-bearing mice,the iron concentration of liver and spleen in control groupincreased 3.36,and 7.92-fold compared to the blank group,respectively(P< 0.001).Administration of ASP the ironconcentration in liver,spleen and tumorreduced by 36.99%,41.71%,and 35.08% compared to the control group,respectively(P< 0.001).3.Effects of ASP on serum ironThe results showed that in each tumor-bearing mice,compared to the blank group the serum iron concentration of the control group reduced 36.12% and 28.13%,respectively(P< 0.001).It was notable that compared to the control group the serum iron level ofASP group increased 1.28 and 1.14-fold,respectively(P< 0.01).Conclusions1.ASP can significantly inhibit the growth of tumor in breast cancer 4T1 cellsand mouse liver cancer H22 cells tumor-bearing mice.2.ASP can significantly reduce tissue iron and increase serum iron.