Nguyen Thai Q, Phan Uyen T T, Can Mao V, Nguyen Dang H, Han Bo, Hoang Ba X
University of Science and Technology of Hanoi, Vietnam Academy of Science and Technology, Hanoi, Vietnam.
Department of Pathophysiology, Military Medical Academy, Hanoi, Vietnam.
Transl Lung Cancer Res. 2025 Jul 31;14(7):2509-2521. doi: 10.21037/tlcr-2024-1272. Epub 2025 Jul 25.
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 lung cancer models.
Immunodeficient BALB/c nude mice (Foxn1nu) were utilized for assessment of anticancer activity. Human lung cancer cells (A549) were injected into the nude mice. When the tumor volume reached 50 mm, 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.
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.
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.
肺癌仍然是全球癌症相关死亡的主要原因之一。最近的研究表明，芬苯达唑（FZ）即使在微摩尔剂量下也显示出有前景的抗癌潜力，但在一些患者中会导致肝毒性。二氯醋酸二异丙胺或维生素B15（DADA），以其肝脏保护特性而闻名，也已证明具有抗肿瘤特性，并且可能减轻FZ诱导的肝损伤。我们的研究旨在评估FZ和DADA在肺癌模型中的协同抗癌作用。
利用免疫缺陷的BALB/c裸鼠（Foxn1nu）评估抗癌活性。将人肺癌细胞（A549）注射到裸鼠体内。当肿瘤体积达到50立方毫米时，将动物随机分为八组，接受单药或联合DADA和FZ治疗。在60天的时间内监测抗肿瘤疗效和毒性。
DADA和FZ改善了BALB/c裸鼠的安全性。在动物模型中，100毫克/千克DADA和40毫克/千克FZ联合治疗导致完全肿瘤消退减少了50%，相比之下，单药治疗组分别为11.1%和0%。与单独的任何一种治疗相比，联合治疗在减小肿瘤大小和诱导肿瘤消失方面显示出更好的疗效。
口服100毫克/千克DADA和40毫克/千克FZ联合治疗可协同抑制移植了A549肺癌细胞的免疫缺陷BALB/c裸鼠的肿瘤生长。有必要进行一项临床研究来证明这种特征明确的药物组合作为肺癌重新利用治疗方法的疗效和安全性。
