The Screening Of Lactobacillus Which Can Suppress Colorectal Cancer And The Research Of Its Mechanism

Colorectal cancer(CRC) is a malignant tumour,and it always occurs in the transition region of colon and rectum.CRC is threatening people's health in China with its increasing morbidity and mortality.There are many elements that can induce CRC,but it is the most important one that daily diet is.A high-protein,high-fat and low-fiber diet can increase the risk of falling in CRC.Although there are some clinical methods to treat CRC,but they have obvious side-effect respectively.It will decrease the quality of life.Probiotics is deemed to a secure food.It is proved that probiotics can give a positive effect on many diseases including cancer.Colon and rectum are not only the tissue which CRC occurs,but also the environment which flora live.So the gut microbiota can touch CRC directly,and it is undoubted that probiotics can have a positive effect on CRC.In recent years,more and more researches focused on the relationship between probiotics and CRC.But there is few study about Lactobacillus plantarum which is one kind of probiotics inhibits CRC.What's more,the mechanism that probiotics inhibit CRC is not clear now.A possible one is that probiotics could regulate some signaling pathways related CRC and Notch signaling pathway is an important one in those signaling pathways.This study focused on Lactobacillus plantarum.After finding out some specific strains of Lactobacillus plantarum which can inhibit CRC in vitro,this study proved it in animal experiment.Regarding Notch signaling pathway as emphasis,explore the mechanism that probiotics inhibit CRC.This study used different strains to irritate HT-29 cell which is a colon cancer cell strain,and then evaluated the change of m RNA expression by q RT-PCR.Four Lactobacillus plantarum strains which had signally different ability to regulate Notch signaling pathway had been found out.After that,animal experiment was used to verify the result.Mice which was induced to CRC by AOM-DSS method were adminisitered by the four strains,L.GG and E.coli.The result including the number of tumour,serum cytokine and histological section showed that the four Lactobacillus plantarum strains could suppress CRC and there were obvious difference between them.To research the mechanism of inhibiting CRC,this study measure the m RNA expression of some signaling pathways related cancer,the structure of gut microbiota and the concentration of short-chain fatty acids in feces.What is more,the different ability to inhibit CRC between live bacteria and dead one was also observed.Accroding to the result,the best strain Lactobacillus plantarum F17 could lower the level of butyrate acid to down-regulate Notch signaling pathway,and then the tumour is suppressed.Other strains have their own ways to suppress CRC respectively,and the effect is also different.At last,this study observed the relationship between cell experiment and animal experiment to try to link them.With PCA and PCC,it is proved that using Hes1 m RNA expression in HT-29 cell can screen the specific strain which could inhibit CRC effectively.In summary,this study found out a specific Lactobacillus plantarum F17 which can suppress CRC signally and one of its possible mechanism was be found out.Besides,this study established a method to mine some specific lactobacillus which have the potential to suppress CRC.