The Effect Of Inflammatory Bowel Disease On The Lung Metastases Of Breast Cancer

Objectives In order to investigate whether inflammatory bowel disease(IBD)can accelerate the progress of breast cancer lung metastasis,we established the mouse model of IBD accompanied with breast cancer lung metastasis,and explored possible mechanism involved in.This work will provide new intervention strategies for the patients who have breast cancer with IBD.Methods 1 The IBD mouse model induced by 2.5% dextran sulfate sodium(DSS)was established on female Balb/c mouse according to our preliminary study.On the basis of this model,the lung metastasis of breast cancer was established by inoculating mouse breast cancer cells 4T1 100ul(1 × 106/ml)by tail vein.Animal experiment results were repeated at 2 times,and there are at least 10 mice in each group(5 animals were selected from each group for statistical analysis).2 The colonic inflammation and the metastasis nodes of lung in the IBD breast cancer lung metastasis model were observed by Hematoxylin-eosin staining.3 The proportion and quantity of neutrophils in peripheral blood were detected by flow cytometry and blood cell counting.Immunohistochemical staining was used to detect the infiltration of neutrophils in lung.4 DNase-I was used to destruct the structure of neutrophil extracellular trap(NET)and Hematoxylin-eosin staining was used to evaluate the lung metastasis nodes.5 Statistical analyses were performed with SAS9.1,Measurement data were expressed as Mean ± standard deviation(SD).The significant differences between the two groups were analyzed by t test.The significant difference between the two groups was analyzed by one-way ANOVA single factor analysis of variance.The Bonferroni method was used to compare the two groups.In the analysis of inflammatory cell infiltration and tissue destruction,the Wilcoxon rank sum test was used between the two groups of samples(grouped design data for multivariate ordered variables).P<0.05 was considered statistically significant.Results 1 2.5% DSS could induce inflammatory reaction of Balb/c female mice obviously.During the course of the experiment,it was observed that DSS-induced mice had obvious blood stool,and the colon were obviously congested and the length were obviously shortened(P<0.01),and a large number of infiltrated-inflammatory cells and damaged-tissues were observed by Hematoxylin-eosin staining.2 In the IBD breast cancer lung metastasis model,the metastasis nodes of lung were significantly more than the control(P<0.01).3 The proportion and quantity of neutrophils in peripheral blood and in lung were increased observed by flow cytometry(P<0.05)?blood cell counting(P<0.05)and immunohistochemical staining(P<0.01).4 The DNase-I destroyed the structure of NET,leading to a decreasing lung metastasis nodes induced by DSS(P<0.05).Conclusions The IBD of female Balb/c mouse induced by DSS can accelerate the lung metastasis progress of breast cancer.The potential mechanism may be that the DSS can induce the mobilization of neutrophils and stimulate the formation of NET to capture the breast cancer cells.The DNase-I disintegrates the NET structure,abandons the prometastasis features of neutrophils in DSS-induced IBD model.