Han Yuehua, Liu Shiyao, Zhu Juan, Liu Peipei, Meng Zixuan, Li Yongping, Li Shanshan, Fan Fangtian, Zhang Mengxiao, Liu Hao
School of Pharmacy, Bengbu Medical University, Bengbu, China.
School of Pharmacy, Bengbu Medical University, Bengbu, China; Anhui Province Engineering Technology Research Center of Biochemical Pharmaceutical, Bengbu, China.
Eur J Pharmacol. 2025 Feb 5;988:177221. doi: 10.1016/j.ejphar.2024.177221. Epub 2024 Dec 20.
In recent decades, significant advancements have been achieved in non-small cell lung cancer (NSCLC) treatment. However, drug resistance, postoperative recurrence, distant metastasis, and other critical issues arise during NSCLC treatment. Natural products play a crucial role in the development of anti-tumor drugs. Halofuginone (HF) is a derivative of Febrifugine, an extract of Dichroa febrifuga Lour, a traditional Chinese medicine. Recent studies on HF have demonstrated its antitumor activity and great potential for clinical applications. However, its antitumor effects and mechanisms in NSCLC remain unknown. This study aimed to elucidate the antitumor effect of HF on NSCLC and preliminarily explore its mechanism of action. The proliferation-related assay revealed that HF could inhibit the proliferation of lung adenocarcinoma cells HCC827 and H1975. Network pharmacology of HF and NSCLC indicated that HF could induce cellular oxidative stress, and the antitumor effect was related to autophagy, apoptosis, and cell cycle arrest. Experimental analysis using flow cytometry and western blotting confirmed that HF indeed induced autophagy, enhanced apoptosis, and caused cell cycle arrest. The addition of N-acetyl-cysteamine acid inhibits the HF-induced increase in reactive oxygen species levels, inhibits autophagy and apoptosis, and alters cell cycle distribution. The HCC827 transplantation tumor animal model established that HF substantially inhibited the growth of transplanted tumors. These findings suggest that HF exerts a significant inhibitory effect on NSCLC in vivo and in vitro. The inhibitory effect of HF on NSCLC was associated with the increase of ROS in tumor cells, induction of autophagy and apoptosis, and cell cycle arrest.
近几十年来，非小细胞肺癌（NSCLC）治疗取得了重大进展。然而，在NSCLC治疗过程中出现了耐药、术后复发、远处转移等关键问题。天然产物在抗肿瘤药物的开发中发挥着关键作用。卤夫酮（HF）是从中药常山提取物常山碱中提取的一种衍生物。最近对HF的研究表明了其抗肿瘤活性和巨大的临床应用潜力。然而，其在NSCLC中的抗肿瘤作用及机制仍不清楚。本研究旨在阐明HF对NSCLC的抗肿瘤作用，并初步探讨其作用机制。增殖相关检测显示，HF可抑制肺腺癌细胞HCC827和H1975的增殖。HF与NSCLC的网络药理学研究表明，HF可诱导细胞氧化应激，其抗肿瘤作用与自噬、凋亡和细胞周期阻滞有关。流式细胞术和蛋白质免疫印迹法的实验分析证实，HF确实可诱导自噬、增强凋亡并导致细胞周期阻滞。添加N-乙酰半胱氨酸可抑制HF诱导的活性氧水平升高，抑制自噬和凋亡，并改变细胞周期分布。建立的HCC827移植瘤动物模型表明，HF可显著抑制移植瘤的生长。这些发现表明，HF在体内和体外对NSCLC均有显著的抑制作用。HF对NSCLC的抑制作用与肿瘤细胞中活性氧增加、自噬和凋亡的诱导以及细胞周期阻滞有关。
