Abstract 175P
Background
Lactobacillus paracasei is known to confer health benefits to humans. Based on our previous 16s rRNA sequencing data, Lactobacillus paracasei was depleted in gastric tumor tissues. Here, we aimed to investigate whether this bacteria could act as a prophylactic for gastric cancer (GC).
Methods
Lactobacillus paracasei ZJUZ2-3 (L.paracasei ZJU2-3) was isolated from a GC patient normal tissues with verification by whole genome sequencing. The antitumor effects of L. paracasei ZJUZ2-3 were assessed in cultured gastric cancer cells and in nude mice models of subcutaneous injected GC cell. The tumor-suppressive metabolite produced by L. paracasei ZJUZ2-3 was identified by ELISA.
Results
L. paracasei was depleted in tumor tissues of patients with GC. A new L. paracasei strain was isolated from normal tissues of a GC patient and nomenclated as L. paracasei ZJUZ2-3. We found that L. paracasei ZJUZ2-3 introtumoral injection suppressed GC tumourigenesis in nude mice. Coincubation with L. paracasei ZJUZ2-3 or its conditioned medium promote the proliferation of GC cells. However, heat-killed L. paracasei ZJUZ2-3 lost its tumor-supressive effect. Indole-3-acetic acid (IAA) was identified as the critical metabolite produced by L. paracasei ZJUZ2-3, and was increased in the GC cells supernatant of cocultrued with L. paracasei ZJUZ2-3 detected by ELISA. IAA metabolited by L. paracasei ZJUZ2-3 inhibited cell proliferation, lowered colony formation of cultured GC cells and inhibit the subcutaneous tumor in nude mice. As aryl hydrocarbon receptor (AHR) ligand, IAA can activate AHR competitively bind MTDH to inhibit its phosphorylation, thus inhibit GC cells nuclear factor kB (NF-kB) signaling pathway. Consistently, when the AHR was inhibited or knockdown, the antitumor effect of IAA was impaired.
Conclusions
L. paracasei ZJUZ2-3 is a novel prophylactic for GC prevention in vitro and in vivo. The tumor-suppressive effect of L. paracasei ZJUZ2-3 is mediated by its metabolite IAA.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
The National Natural Science Foundation.
Disclosure
All authors have declared no conflicts of interest.