Melatonin boosts BCG immunotherapy against bladder cancer in mouse models.

Melatonin boosts BCG immunotherapy against bladder cancer in mouse models.

BCG (Bacillus Calmette-Guérin) intravesical immunotherapy is the standard adjuvant treatment for non-muscle-invasive bladder cancer but has efficacy limitations and recurrence. This study tested whether melatonin could enhance BCG's anti-tumor effects in a murine bladder cancer model.

Combining high-dose BCG with melatonin (HDBCG+MLT) reduced tumor weight and volume compared to either BCG or melatonin alone. The combination increased apoptosis and immune cell infiltration, reduced blood vessel formation (angiogenesis), and suppressed EMT (epithelial-mesenchymal transition)—a metastasis-promoting process. Melatonin also attenuated BCG-induced systemic inflammation (elevated WBC, CRP).

Melatonin appears to enhance BCG efficacy while reducing its pro-inflammatory side effects—a potentially beneficial combination if validated in humans.

Key Findings

• HDBCG+MLT combination reduced tumor weight and volume vs. either agent alone
• Melatonin increased apoptosis and immune cell infiltration while reducing micro-vessel density
• BCL-2 downregulated; BAX, p53, IFN-γ upregulated with combination
• Melatonin attenuated BCG-induced increases in WBC and CRP
• Combination suppressed VEGF-A, HIF-1α, and EMT pathway markers

Implications

Melatonin may be a low-toxicity adjunct to BCG therapy for bladder cancer, potentially improving efficacy and reducing systemic inflammation. Clinical trials exploring this combination would be warranted based on promising preclinical results.

Caveats

Murine xenograft model; abstract-only. Results may not translate to human bladder cancer. Optimal melatonin dosing and timing relative to BCG instillation requires definition. Safety in patients with concurrent conditions needs evaluation.

Source: Molecular biology reports — 2026-04-10