Investigate the relationship between Bacillus coagulans and its inhibition of chemotherapy‐induced lung cancer resistance.

Lung cancer is a leading cause of death globally, with lung adenocarcinoma being the most common subtype. Despite advancements in targeted therapy, drug resistance remains a major challenge. This study investigated the impact of <italic>Bacillus coagulans</italic> on drug resistance in lung adenocarcinoma cells. The cells were pretreated with <italic>B. coagulans</italic> culture filtrate (BCCF), and functional assays were performed, including cell proliferation, cell cycle, apoptosis, and immunofluorescence staining. Results showed that BCCF induced cell cycle arrest at the S phase, reducing cell proliferation and suppressing drug resistance marker P‐glycoprotein expression in BCCF‐treated resistant cells rather than BCCF‐treated control cells. Moreover, drug‐resistant cells exhibited the ability for epithelial‐mesenchymal transition, which could contribute to their necrosis through the iron‐mediated cell death pathway upon BCCF treatment. Proteomic analysis identified downregulation of DNA mismatch repair protein PMS2 after BCCF treatment. These findings suggest that <italic>B. coagulans</italic> may modulate the DNA repair pathway, influencing drug resistance in lung adenocarcinoma cells. In conclusion, this study highlights the potential impact of <italic>B. coagulans</italic> on drug‐resistant lung adenocarcinoma cells. Further investigation and understanding of the regulatory mechanisms by which <italic>B. coagulans</italic> modulates drug resistance in lung adenocarcinoma can aid in the development of more effective treatment strategies to improve the prognosis of lung cancer patients. [ABSTRACT FROM AUTHOR]