Inhibition Of Human Gastric Cancer By Nano-Fe₃O₄-LTA And Nano-Fe₃O₄-EPS From Bifidobacterium

Objective: To explore the inhibition effect of Nano-sized-Fe₃O₄-Lipoteichoicacid(LTA) from and Nano-sized-Fe₃O₄-extracellular polysaccharides(EPS) from Bifidobacterium on experimental gastric cancer in vivo and the pathway of antitumor.Methods: Nude mices subcutaneously transplated with BGC823 human gastric cancer cells were completely random divided into the two major groups:â‘´the Nano-sized-Fe₃O₄-Lipoteichoicacid group:the negative group, which was administered with normal saline. The positive group, which was administered with Cyclophosphamide Tablets(CY).The experimental groups,which were administered with different dose of Nano-sized-Fe₃O₄-LTA. The LTA group, which was administered with LTA.⑵the Nano-sized-Fe₃O₄- extracellular polysaccharides group:the negative group, which was administered with normal saline. The positive group, which was administered with Cyclophosphamide Tablets(CY).The experimental groups,which were administered with different dose of Nano-sized-Fe₃O₄-EPS. The EPS group, which was administered with EPS. The positive group was administered each-five-day, other groups were administered each-two-day. The long and short diameters were measure every four days, and the growth curve of transplanted tumor was measured. The tumor inhibitory rates were calculated at the same time. The production of NO and iNOS of nude mice peritoneal macrophages were assessed by Griess reaction. The expression level of vascular endothelial growth factor(VEGF),Survivin and tumor associated macrophages(TAMs) of gastric cancer were detected by using immunohistochemical method.Results:The Nano-sized-Fe₃O₄-Lipoteichoicacid group:1.The inhibitory effects of Nano-sized-Fe₃O₄-LTA from bifidobacterium on human gastric cancer in nude mice: After been treated with different dose of Nano-sized-Fe₃O₄-LTA, the growth rates of the transplanted tumors were slowed down respectively. In the mice treated with low-, medium-dose Nano-sized-Fe₃O₄-LTA, the growth inhibition rates of tumor were 49% and 42%, the growth inhibition rates of tumor with high-dose Nano-sized-Fe₃O₄-LTA was only 34%. It illustrates the changes in concentration of the anti-tumor dose is connected with the inhibition effect on tumor.2.Side-effect and weight changes of tumor-loaded mice administrated by Nano-sized-Fe₃O₄-LTA: Contract from CY group, the weight of mice in each dosage group of Nano-sized-Fe₃O₄-LTA and NS group grow steadily, and the need of feeds is fixable. However, with the apparent inhibitory effect on tumor, the weight of mice in CY group descent rapidly and happened with disgorging and digestive apparatus disordered even dead.3.Griess reaction assay the contents of by macrophages: Contracting to NS group, Nano-sized-Fe₃O₄-LTA can activate the macrophages to secrete NO and iNOS to more high degree(p<0.01);Besides the CY group, Nano-sized-Fe₃O₄-LTA low dosage group irritate macrophages to secrete NO and iNOS level more than other groups(P<0.05).The relationship between the dosage of Nano-sized-Fe₃O₄-LTA and NO and iNOS level is up-adjustion.4.Contents of VEGF, Survivin and TAMs in transplanted tumors detected by Immunohistochemical staining: Contracting to NS group, the VEGF and TAMs density by different dosages of Nano-sized-Fe₃O₄-LTA are significantly lower (P<0.01). Contracting to NS group, the Survivin density by different dosages of Nano-sized-Fe₃O₄-LTA are lower (P<0.05).The contents of VEGF, Survivin and TAMs by the low dosage of Nano-sized-Fe₃O₄-LTA are lower than the contents of VEGF, Survivin and TAMs by the dosage of LTA(P<0.05). The dosage of Nano-sized-Fe₃O₄-LTA is closely related to contents of VEGF, Survivin and TAMs in transplanted tumors.The Nano-sized-Fe₃O₄-extracellular polysaccharides group:1.The inhibitory effects of Nano-sized-Fe₃O₄-EPS from bifidobacterium on human gastric cancer in nude mice: After been treated with different dose of Nano-sized-Fe₃O₄-EPS, the growth rates of the transplanted tumors were slowed down respectively. In the mice treated with high dose Nano-sized-Fe₃O₄-EPS, the growth inhibition rates of tumor was 46%, the tumor growed slowly.The growth inhibition rates of tumor with low-dose Nano-sized-Fe₃O₄-EPS was only 21%. It illustrates the changes in concentration of the anti-tumor dose is connected with the inhibition effect on tumor.2.Side-effect and weight changes of tumor-loaded mice administrated by Nano-sized-Fe₃O₄- EPS: Contract from CY group, the weight of mice in each dosage group of Nano-sized-Fe₃O₄- EPS and NS group grow steadily, and the need of feeds is fixable. However, with the apparent inhibitory effect on tumor, the weight of mice in CY group descent rapidly and happened with disgorging and digestive apparatus disordered.3.Contents of VEGF, Survivin and TAMs in transplanted tumors detected byImmunohistochemical staining: Contracting to NS group, the VEGF and TAMs density by different dosages of Nano-sized-Fe₃O₄-EPS are significantly lower (P<0.01). Contracting to NS group, the Survivin density by different dosages of Nano-sized-Fe₃O₄-EPS are lower (P<0.05). The contents of VEGF, Survivin and TAMs by the high dosage of Nano-sized-Fe₃O₄-EPS are lower than the contents of VEGF, Survivin and TAMs by the dosage of EPS (P<0.05). The dosage of Nano-sized-Fe₃O₄-EPS is closely related to contents of VEGF, Survivin and TAMs in transplanted tumors.Conclusion: Nano-sized-Fe₃O₄-bifidobacterium-LTA and Nano-sized-Fe₃O₄-bifidobacterium-EPS exert an inhibiting effect on the growth of human gastric cancer in nude mice. The mechanisms could be as follows:â‘´Activing the immunity inhibiting the proliferation and activating the immune cells such as macrophages to secrete tumor associate cytokines to inhibit the proliferation of tumor cells.⑵Decrease the expression of VEGF,Survivin and TAMs and inhibit the angiogenesis of human gastric cancer.⑶Nano-sized-Fe₃O₄ to be a carrier, LTA and EPScan get more permeability and improve the therapy effect.