| Colon cancer,a malignant tumor of digestive tract,has become the third most common cancer after lung cancer and breast cancer and the second leading cause of cancer death.The main treatment methods of colon cancer include surgery,chemical drugs and radiotherapy.These treatment methods can significantly improve the survival rate of patients with colon cancer,but they could cause obvious side effects such as nausea,vomiting and inflammatory enteritis,which will affect the life quality of patients.At present,a large amount of evidence shows that probiotics,especially Lactobacillus,as a member of intestinal microbiota,could enhance body’s immunologic function,regulate the composition and structure of intestinal flora,enhance the efficacy of radiotherapy,chemical drugs and chemotherapy,so as to play an important role in the prevention and treatment of colon cancer.Therefore,it is a new strategy to supplement specific probiotics and adjuvant carbon ion radiotherapy for colon cancer.In this paper,the characterizations of probiotics indicate that JY300-8 holds highest hydrophobicity,self cohesion and strong anti Helicobacter pylori ability,and the prevention and treatment effect of colon cancer model mice induced by CT-26 cells was evaluated.Lactobacillus reuteri JMR-01 was isolated from the intestinal tract of breast cancer mice achieving complete response during JY300-8 adjuvant carbon ion radiotherapy.Compared with JY300-8,JMR-01 had stronger inhibitory effect on CT-26 cell proliferation.In order to further improve the therapeutic effect of probiotics on colon cancer,the experiment of JMR-01 adjuvant carbon ion radiotherapy on colon cancer mice model induced by CT-26 cells and its mechanisms were carried out,The main research results of this paper are as follows:(1)Characterizations of probiotic properties.Through the study on the performance of acid and bile salt tolerant probiotic mutant strains,it was found that JY300-8 had the highest hydrophobicity,self aggregation ability and anti Helicobacter pylori ability,indicating that it holds the best prebiotic properties.At 24 h,JY300-8 had the highest co-aggregation rate and the highest inhibition rate of urease activity of Helicobacter pylori,reaching 64.4% and 62.3% respectively.The results showed that JY300-8 could reduce the colonization of pathogenic bacteria in the intestinal tract by inhibiting the urease activity of Helicobacter pylori,on the other hand,it could coaggregate with Helicobacter pylori to remove pathogenic bacteria.(2)Evaluation of the preventive and therapeutic effect of probiotics on colon cancer mice model induced by CT-26 cells.The prevention and treatment of JY300-8 on colon cancer mice model induced by CT-26 cells showed that the prevention rates of JY300-8 live bacteria and inactivated bacteria were 31% and 24.2% respectively,which were higher than those of commercial probiotics(Mixture of lyophilized powder of Lactobacillus rhamnosus,Bifidobacterium lactis and Bifidobacterium animalis)with 13.9% inhibition rate.In the first 21 days of treatment with probiotics,the tumor volume of mice in living bacteria group and inactivated bacteria group were significantly lower than that in PBS tumor control group and commercial probiotics group(P < 0.05).In the 21-55 days of treatment with probiotics,the tumor volume of mice in JY300-8 living bacteria group and the inactivated bacteria group were not significantly different from that in the PBS tumor control group.The results showed that JY300-8 living and inactivated bacteria could effectively prevent colon cancer and played an important role in the early treatment of colon cancer model mice,but the effect was not obvious in the late treatment of colon cancer mice model.Therefore,it is very important to develop probiotics that can effectively treat colon cancer.(3)Optimization of probiotics for efficient inhibition of colon cancer cells.By comparing the inhibitory effects of JY300-8 and JMR-01 on the proliferation of CT-26 cells in vitro,it was found that when the ratio of JMR-01 to CT-26 cells(cfu:cells)was 1:1 at 24 h,the inhibitory effect of JMR-01 on the proliferation of CT-26 was 28.4%,significantly higher than that of JY300-8,and the inhibitory rate of JY300-8:CT-26=50:1 on the proliferation of CT-26 was only 16.02%.By optimizing the combination of JMR-01 live bacteria and inactivated bacteria,it was found that the highest inhibitory effect on the proliferation of CT-26 cells was achieved when the ratio of JMR-01 live bacteria to inactivated bacteria was 1:1,and the inhibition rate reached 39.55%.The combination could be used in the experiment of adjuvant carbon ion radiotherapy in colon cancer model mice.(4)Evaluation of the effect of probiotics adjuvant carbon ion radiotherapy on colon cancer mice model induced by CT-26 cells.In order to further improve the therapeutic effect of colon cancer,the effect of JMR-01 adjuvant carbon ion therapy on colon cancer mice model was evaluated.The results showed that the survival rates of 12C6+ irradiation + live bacteria + inactivated bacteria(IR + LP + IP)group and 12C6 + irradiation + inactivated bacteria(IR + IP)group were 71.4% after 50 days.But IR + LP + IP group had complete response mice,and complete response rate was 14.3%,indicating that JMR-01 LP + IP adjuvant carbon ion irradiation could improve the therapeutic effectiveness of colon cancer.The results provide a new strategy for the treatment of colon cancer.(5)Study on the mechanisms of JMR-01 adjuvant carbon ion to improve the therapeutic effectiveness of colon cancer.By measuring the activity of fecal Nitroreductase,the abundance of fecal intestinal flora and the content of short chain fatty acids of control group and experimental groups,it was found that IR + LP + IP intervention could significantly reduce the activity of fecal Nitroreductase,decrease the abundance of harmful bacteria related to colon cancer,such as Bacteroides fragilis and Clostridium perfringens,increase the abundance of beneficial bacteria such as Lactobacillus and Bifidobacterium,and effectively enhance the content of acetic acid and propionic acid.In addition,by detecting the effects of JMR-01 LP,IP and LP + IP on splenocyte proliferation and macrophage phagocytosis,it was found that LP + IP had the greatest promoting effect on splenocyte proliferation and macrophage phagocytosis,which was helpful to enhance the nonspecific immune function of the body.JMR-01 adjuvant carbon ion radiotherapy can improve the therapeutic effect of colon cancer by regulating intestinal flora and enhancing nonspecific immunity. |
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