Cai Bao-Ning, Ma Bo, Zhang Sheng, He Wei
General Hospital of Ningxia Medical University, Yinchuan, 750001, Ningxia, P. R. China.
General Thoracic Surgery, General Hospital of Ningxia Medical University, No. 804 Shengli South Street, Xingqing District, Yinchuan, 750001, Ningxia, P. R. China.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Jan 29. doi: 10.1007/s00210-025-03810-y.
Monotropein (Mon) is an iridoid glycosides extracted from Morinda officinalis F.C. How. (Rubiaceae) that shows anticancer effects on colorectal cancer. This study aimed to investigate the therapeutic effect of Mon on lung cancer. The viability, apoptosis, invasion, and tube formation of A549 and H1299 were determined by CCK8 assay, flow cytometry, transwell assay, and tube formation assay. NF-κB expression in the nucleus was detected by immunofluorescent staining. In vivo assay, BALB/c nude mice were divided into a sham group and a 2 mg/kg Mon group. For the Mon group, mice were orally administered with 2 mg/kg Mon. The duration of the animal study was 35 days, and the tumor formation and angiogenesis were investigated. Compared with the control (Mon 0 μM) group, Mon dramatically repressed the viability, invasion, tube formation, proliferation marker Ki67, N-cadherin, and VEGFA expressions in A549 cells (Mon of 25, 50, and 100 µM) and H1299 cells (Mon of 50 and 100 µM). Mon dramatically promoted cell apoptosis, cleaved caspase 3, and E-cadherin expressions. Besides, Mon remarkably downregulated p-AKT and p-NF-κB protein expressions. Moreover, AKT agonist SC79 reversed the anticancer effects of 100 µM Mon on A549 cells. Furthermore, Mon markedly suppressed tumor growth, decreased N-cadherin, VEGFA, p-AKT, and p-NF-κB expressions, increased apoptosis and E-cadherin expression, and SC79 reversed the inhibition effects of Mon in vivo. Thus, Mon is a potential antitumor natural drug, and more signaling pathways involved in Mon-modulated lung cancer progression are worth testing for further investigation.
巴戟天寡糖（Mon）是从巴戟天（茜草科）中提取的一种环烯醚萜苷，对结直肠癌具有抗癌作用。本研究旨在探讨Mon对肺癌的治疗效果。通过CCK8法、流式细胞术、Transwell法和管腔形成实验分别检测A549和H1299细胞的活力、凋亡、侵袭及管腔形成情况；采用免疫荧光染色检测细胞核中NF-κB的表达。在体内实验中，将BALB/c裸鼠分为假手术组和2mg/kg Mon组，Mon组小鼠口服给予2mg/kg Mon。动物实验为期35天，观察肿瘤形成及血管生成情况。与对照组（Mon浓度为0μM）相比，Mon显著抑制A549细胞（Mon浓度为25、50和100μM）和H1299细胞（Mon浓度为50和100μM）的活力、侵袭、管腔形成、增殖标志物Ki67、N-钙黏蛋白及VEGFA的表达；显著促进细胞凋亡、裂解的caspase 3及E-钙黏蛋白的表达。此外，Mon显著下调p-AKT和p-NF-κB蛋白表达。而且，AKT激动剂SC79可逆转100μM Mon对A549细胞的抗癌作用。此外，Mon显著抑制体内肿瘤生长，降低N-钙黏蛋白、VEGFA、p-AKT和p-NF-κB的表达，增加凋亡及E-钙黏蛋白表达，而SC79可逆转Mon在体内的抑制作用。因此，Mon是一种潜在的抗肿瘤天然药物，更多参与Mon调控肺癌进展的信号通路值得进一步研究验证。
