OBJECTIVE  To use the Lewis lung cancer xenograft mouse model as the research subject, combining in vivo and in vitro experiments to investigate the potential ameliorative effects of fermented Astragali Radix membranaceus on lung cancer.

METHODS  A total of 40 C57BL/6 mice were randomized into 5 groups: Control group, model group, Astragali Radix extract group, fermented Astragali Radix group, and positive drug group(cisplatin), which were administered for 3 weeks after subcutaneous injection of lung cancer cells. The body weight, tumor volume, tumor inhibition rate and organ index of mice were calculated, the pathological changes of tumor, liver, kidney and spleen were observed, and the changes of serum immune cytokines, gut microbiota and short-chain fatty acids were detected. The effects of the Astragali Radix extract, fermented Astragali Radix, the fecal metabolites of Astragali Radix extract group, and the fecal metabolites of fermented Astragali Radix group were also evaluated on the proliferation rate of tumor cells using LLC cells in vitro.

RESULTS  The results showed that fermented Astragali Radix had obvious anti-cancer effect, with a tumor suppression rate of 47.2%. Fermented Astragali Radix also had a protective effect on liver, kidney, and spleen, could prevent histopathological damage of these organs and restore spleen index and thymus index, while lowering the serum levels of IL-1β, TNF-α, IFN-γ, TGF-β, and IL-6 and increasing the level of IL-12. Additionally, fermented Astragali Radix regulated the gut microbiota of lung cancer mice, reducing harmful bacteria or potential pathogens such as Prevotella, Oscillospira, and Bacteroides, and increasing the beneficial bacteria such as Lactobacillus, Bifidobacterium, Turicibacter, and specifically enriching Akkermansia. Fermented Astragali Radix also promoted the production of short chain fatty acids such as acetic acid and valeric acid in the intestines of mice with lung cancer. In vitro studies showed that low, medium and high concentrations(20, 40, 80 μg·mL⁻¹) of fermented Astragali Radix had a certain direct inhibitory effect on LLC cells, with cell proliferation rates of 80.58%, 72.05% and 69.02%, respectively. The fecal metabolites of fermented Astragali Radix group reduced LLC cell proliferation rate to 47.60%, which showed a stronger LLC cell inhibitory ability.

CONCLUSION The ability of fermented Astragali Radix to improve lung cancer is partly dependent on gut microbiota, and the indirect inhibition of gut microbial metabolism is the main way. Fermented Astragali Radix has the potential to play a role in the prevention and treatment of lung cancer as an intestinal microecological regulator.