Abstract
BACKGROUND: Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Recent studies suggest that fenbendazole (FZ), even at micromolar doses, shows promising anticancer potential but can cause liver toxicity in some patients. Diisopropylamine dichloroacetate or vitamin B15 (DADA), known for its hepatoprotective properties, has also demonstrated antitumor properties and may reduce FZ-induced liver injury. Our research aimed to evaluate the synergistic anticancer effects of FZ and DADA in vivo lung cancer models. METHODS: Immunodeficient BALB/c nude mice (Foxn1nu) were utilized for in vivo assessment of anticancer activity. Human lung cancer cells (A549) were injected into the nude mice. When the tumor volume reached 50 mm(3), the animals were randomized into eight groups, receiving either single or combined DADA and FZ treatments. The antitumor efficacy and toxicity were monitored over a 60-day period. RESULTS: DADA and FZ improved the safety profiles in BALB/c nude mice. In the animal model, combined treatment with 100 mg/kg DADA and 40 mg/kg FZ resulted in a 50% reduction in complete tumor regression, compared to 11.1% and 0% in the single-agent treatment groups, respectively. The combination therapy showed superior efficacy in reducing tumor size and inducing tumor loss compared to either treatment alone. CONCLUSIONS: Combining oral treatment of 100 mg/kg DADA and 40 mg/kg FZ synergistically inhibited tumor growth in immunodeficient BALB/c nude mice transplanted with A549 lung cancer cells. A clinical study is warranted to prove the efficacy and safety of this well-characterized drug combination as a repurposing treatment for lung cancer.