Introduction: A number of factors can limit the efficacy of cisplatin as a chemotherapeutic agent for lung cancer. An animal model of Lewis lung cancer (LLC) has been studied to examine the role of gut microbes, specifically Akkermansia muciniphila, in enhancing the effects of cisplatin on tumor growth.
Methods: Sixty C57BL/6 mice were injected with LLC cells and then randomized into four groups: control, cisplatin alone (3 mg/kg), A. muciniphila alone (109 CFU/mL), and cisplatin combined with A. muciniphila. Treatments were administered intraperitoneally (cisplatin) and orally (A. muciniphila) for four weeks. Tumor volumes were measured every three days using calipers. At the end of the treatment period, tumors were excised and weighed. Blood and tissue samples were collected for cytokine analysis (IL-6 and TNF-α) and immunohistochemistry to assess immune cell infiltration (CD8+ T cells). Statistical analysis involved ANOVA and Tukey's post hoc test for multiple comparisons.
Results: The combination group showed a significantly greater reduction in tumor volume (mean decrease of 65.2 ± 4.8%) compared to the cisplatin alone group (mean decrease of 45.3 ± 3.5%, p < 0.01) and the A. muciniphila alone group (mean decrease of 20.1 ± 2.7%, p < 0.001). Tumor weight was significantly lower in the combination group (mean 0.75 ± 0.12 g) than in the cisplatin alone group (mean 1.30 ± 0.15 g, p < 0.01) and the A. muciniphila alone group (mean 1.85 ± 0.20 g, p < 0.001). Cytokine analysis revealed significantly lower levels of IL-6 and TNF-α in the combination group compared to other groups (p < 0.05). Immunohistochemistry showed increased infiltration of CD8+ T cells in tumors from the combination group.
Conclusion: The results of this study offer a promising avenue for cancer treatment. By enhancing the anti-tumor efficacy of cisplatin, Akkermansia muciniphila could potentially revolutionize the way we approach chemotherapy. These findings inspire hope for improved therapeutic outcomes when probiotics are combined with chemotherapy.