Lactobacillus brevis YNH inhibits proliferation of HeLa cells and promotes their apoptosis by modulating the PI3K/AKT pathway.

Abstract

Introduction: Existing treatments for cervical cancer have side effects on the human body. Some lactobacilli inhibit tumour progression in a strain-specific manner without toxic side effects.

Material and methods: We explored whether Lactobacillus brevis YNH isolated from the vagina has anti-cervical cancer effects by performing Cell Counting Kit-8 assays, flow cytometry, JC-1 staining, and western blotting. Transcriptome sequencing was performed to determine the possible mechanism. Xenograft tumour model mice that were orally administered Lactobacillus brevis YNH were used to validate the anticancer effects in vivo.

Results: Our study revealed that Lactobacillus brevis YNH downregulated the expression of cyclin E1 and CDK2, resulting in cell cycle arrest at S phase and inhibition of HeLa cell proliferation. In addition, HeLa cells treated with Lactobacillus brevis YNH significantly promoted the cleavage of caspase-3 and caspase-8, and increased the expression of Bax. Also, the mitochondrial membrane potential decreased, which induced apoptosis of HeLa cells. Most of the differentially expressed genes were enriched in the PI3K/AKT pathway, indicating that Lactobacillus brevis YNH might exert its anticancer effects through the PI3K/AKT pathway. Most importantly, we found that the tumour volume of mice was significantly smaller than control group after orally administered Lactobacillus brevis YNH, and biochemical results showed that Lactobacillus brevis YNH had no toxic side effects on the liver or kidney, suggesting that Lactobacillus brevis YNH has anti-cervical cancer effects in vivo.

Conclusions: This study revealed the anti-cervical cancer effects of Lactobacillus brevis YNH, providing a new candidate bioactive substance for the treatment of cervical cancer.