Synergistic anti-tumor effect of fenbendazole and diisopropylamine dichloroacetate in immunodeficient BALB/c nude mice transplanted with A549 lung cancer cells.

IF 3.5 2区 医学 Q2 ONCOLOGY
Translational lung cancer research Pub Date : 2025-07-31 Epub Date: 2025-07-25 DOI:10.21037/tlcr-2024-1272
Thai Q Nguyen, Uyen T T Phan, Mao V Can, Dang H Nguyen, Bo Han, Ba X Hoang
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引用次数: 0

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 mm3, 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.

芬苯达唑和二氯乙酸二异丙胺对A549肺癌细胞移植免疫缺陷BALB/c裸鼠的协同抗肿瘤作用。
背景: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),即使是微摩尔剂量,也显示出有希望的抗癌潜力,但在一些患者中可能引起肝毒性。二氯乙酸二异丙胺或维生素B15 (DADA)以其保护肝脏的特性而闻名,也被证明具有抗肿瘤特性,并可能减少fz诱导的肝损伤。我们的研究旨在评估FZ和DADA在体内肺癌模型中的协同抗癌作用。方法:采用免疫缺陷BALB/c裸鼠(Foxn1nu)进行体内抗癌活性评价。将人肺癌细胞A549注射到裸鼠体内。当肿瘤体积达到50 mm3时,将动物随机分为8组,分别接受单一或DADA和FZ联合治疗。在60天的时间内监测抗肿瘤疗效和毒性。结果:DADA和FZ提高了BALB/c裸鼠的安全性。在动物模型中,100 mg/kg DADA和40 mg/kg FZ联合治疗可使肿瘤完全消退减少50%,而单药治疗组分别为11.1%和0%。与单独治疗相比,联合治疗在缩小肿瘤大小和诱导肿瘤消失方面表现出优越的疗效。结论:DADA 100 mg/kg与FZ 40 mg/kg联合口服可协同抑制A549肺癌细胞移植后免疫缺陷BALB/c裸鼠的肿瘤生长。有必要进行临床研究,以证明这种具有良好特征的药物组合作为肺癌重新治疗的有效性和安全性。
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来源期刊
CiteScore
7.20
自引率
2.50%
发文量
137
期刊介绍: Translational Lung Cancer Research(TLCR, Transl Lung Cancer Res, Print ISSN 2218-6751; Online ISSN 2226-4477) is an international, peer-reviewed, open-access journal, which was founded in March 2012. TLCR is indexed by PubMed/PubMed Central and the Chemical Abstracts Service (CAS) Databases. It is published quarterly the first year, and published bimonthly since February 2013. It provides practical up-to-date information on prevention, early detection, diagnosis, and treatment of lung cancer. Specific areas of its interest include, but not limited to, multimodality therapy, markers, imaging, tumor biology, pathology, chemoprevention, and technical advances related to lung cancer.
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