Effect Of Staphylococcus Aureus On The Growth Of S180 Ascites Tumor Mice

Objectives:Malignant tumor is a direct and serious threat to human life and health.Patients are easy to be infected with Staphylococcus aureus(S.aureus),which is one of the most common bacteria infected with malignant tumor.However,few studies have examined the relationship between S.aureus infection and tumor development.Recent studies have shown that infection can also improve survival in cancer patients.One of the reasons for this improved survival rate may be the reactivation of the host immune system’s inflammatory anti-tumor response,in which macrophages are a key player.Macrophages will polarize into macrophages with different phenotypes and functions under different environments.The purpose of this study was to examine in vivo whether S.aureus really can improve the survival rate of cancer patients and how S.aureus affects tumor growth.Methods:1.In this study,S.aureus was used to infect the peritoneal cavity of mouse,and the safest concentration of bacterial solution that could maximize the activation of the immune system of mice was selected as the modeling concentration of peritonitis in mice.2.Survival rate experiment:The experiment was divided into normal saline control group,S.aureus control group(SA group),S180 ascites tumor model group,S.aureus+S180 group(SA+S180 group).SA+S180 group was divided into 9 subgroups due to different time of bacterial infection.S180 tumor cells were injected on day 0,and S.aureus was injected into mice intraperitoneally on days 30,24,12,6,3,0,1,3 and 6,respectively,and then weight was weighed every 3 days.The clinical manifestations and survival status of mice were observed and recorded.3.According to the data of the group with the highest survival rate,the mouse model was repeatedly established with S180 cells as the time starting point,the samples were collected at 0d,1d,6d and 12d.Peritoneal lavage fluid was collected from mice in each group,and the total amount of lavage fluid was recorded.Then peritoneal cells were separated and divided into two parts,one of which was stained by Swiss Giemsa,and the proportion of nucleated cells was counted.In the other,flow cytometry was performed to measure the proportion of CD45~-cells(roughly estimated to be S180 tumor cells).The proportion of M1and M2 type macrophages in peritoneal lavage fluid and spleen cells was analyzed by flow cytometry;The contents of serum Th1-related cytokines IFN-γ,IL-12p70 were determined by CBA.Results:1.By comparing five different concentrations of peritonitis mices,2.0×10~8 bacteria/ml was determined as the optimal concentration of bacterial solution.2.Compared with the S180 model group,the survival rate of mice with ascites tumor in the group infected with S.aureus in advance was significantly higher than those infected with S.aureus later,and the earlier infected with S.aureus after inoculation with S180 tumor cells,the higher the survival rate.3.According to the results of the proportion of tumor cells and CD45~-cells in the Swiss Jimsa staining cell classification and counting,tumor cells in the abdominal cavity of mice in the bf6(12)NS+S180 group began to increase on the6th day,while there was no significant increase in the tumor cells in the bf6(12)SA+S180 group.Peritoneal macrophages of mice in each group increased first,reached a peak on the 6th day,and then decreased.Compared with bf6(12)NS+S180 group,M1-type macrophages in the abdominal cavity of mice in bf6(12)SA+S180 group increased,and could be maintained at a higher level in a certain period of time.Th1-related inflammatory cytokines IFN-γand IL-12p70 also showed corresponding changes.Conclusions:1.S.aureus can effectively inhibit the growth of S180 ascites tumor and improve the survival rate,and the inhibitory effect of S.aureus varies with different infection time.2.The inhibitory effect of S.aureus on S180 ascites tumor was mainly manifested in activating the immune system of the body,and had no obvious direct effect on S180 tumor cells.3.The immune effect induced by S.aureus is mainly dependent on the phagocytosis of proinflammatory macrophages.