SR1001 Inhibits Clostridium difficile Infection by Interfering Phosphorylation of PI3K/AKT/mTOR Pathway / 胃肠病学

ABSTRACT

Background: Clostridium difficile infection (CDI) is the most commonly seen opportunistic infection. Although antibiotic therapy is the first-line treatment, there are still some problems existed such as poor therapeutic effect, recurrence of infection and recrudescence. Therefore, it is necessary to develop new anti-infectious drugs. Aims: To explore the possible intervention effect of SR1001 on CDI and its potential mechanism, and to explore its potential intervention targets. Methods: Clostridium difficile (C. difficile) was cultured with HT-29 cells, and were divided into control group, CDI group (infected with C. difficile) and SR1001 treatment group (infected with C. difficile+SR1001 treatment). Morphological changes of HT-29 cells were observed. Cell proliferation was detected by CCK-8 assay, expression of PI3K/AKT/mTOR signaling pathway was detected by Western blotting, and TcdB content in the cell supernatant was detected by ELISA. Results: Compared with the control group, cells in CDI group became brighter and rounder, apoptosis was obvious, cell proliferation ability was significantly decreased (P<0.05), and inhibition of cell proliferation increased with the extension of time; the expressions of PI3K/AKT/mTOR pathway phosphorylated proteins and the content of TcdB in the supernatant were significantly increased (P<0.05). After SR1001 treatment, the cells tended to be in normal 'paving stone'-like arrangement, apoptosis was improved, cell proliferation ability was significantly increased than in CDI group, and expressions of PI3K/AKT/mTOR pathway phosphorylated proteins and TcdB content in the supernatant were significantly decreased. Conclusions: SR1001 can reverse the effect of C. difficile on growth of colon cancer cells by interfering the phosphorylation of PI3K/AKT/mTOR pathway.