Li Tiantian, Wang Weidong, Zhu Mingwei, Dong Tianxiu, Jiang Jian, Li Zizhuo, An Tingting, Chen Xi, Mao Yingxuan, Chen Yaodong, Yang Xiuhua
Department of Abdominal Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Ultrasonic department, The First Hospital of Qiqihar, Qiqihar, 161000, China.
Discov Oncol. 2025 May 19;16(1):822. doi: 10.1007/s12672-025-02695-w.
Hepatocellular carcinoma (HCC) has the sixth highest morbidity and fourth highest mortality worldwide. Nuciferine (NF) is an aporphine alkaloid isolated from the leaves of Nelumbo nucifera Gaertn that showed good antineoplastic effects in various malignancies. However, the specific effects and mechanisms of NF in HCC are still unclear. The antiproliferative effect of NF was discovered via MTT assays and reconfirmed by performing plate colony formation assays in HCC cells. In addition, the inhibitory activities of NF on the cell cycle and apoptosis in HCC cells were determined through PI/RNase staining and Annexin V-FITC/PI staining detected on a flow cytometer, respectively. Then, the suppressive capacity of NF in vivo was evaluated using multiple modalities of noninvasive ultrasonic imaging and histopathological examination in xenograft HCC tumors. In terms of the mechanisms involved in NF treatment, RNA sequencing (RNA-seq) and bioinformatics analysis were used for predictions, which were further confirmed by employing qRT-PCR analysis. This study demonstrated that NF could exert suppressive effects on the proliferation of HCC cells by arresting the cell cycle at G2 phase. In addition, NF could increase the proportion of apoptotic cells compared with that in the control groups in a concentration-dependent manner. This study certified that NF could suppress the proliferation and cell cycle of HCC cells, while accelerating apoptosis, which was determined to be closely related with the inhibition of the HER2-AKT/ERK1/2 signaling pathway.
肝细胞癌（HCC）在全球发病率排名第六，死亡率排名第四。荷叶碱（NF）是从莲（Nelumbo nucifera Gaertn）叶中分离出的一种阿朴啡生物碱，在多种恶性肿瘤中显示出良好的抗肿瘤作用。然而，NF在HCC中的具体作用和机制仍不清楚。通过MTT试验发现了NF的抗增殖作用，并在HCC细胞中进行平板集落形成试验再次证实。此外，分别通过PI/RNase染色和流式细胞仪检测的Annexin V-FITC/PI染色来确定NF对HCC细胞周期和凋亡的抑制活性。然后，在异种移植HCC肿瘤中，使用多种非侵入性超声成像和组织病理学检查方法评估NF在体内的抑制能力。在NF治疗涉及的机制方面，使用RNA测序（RNA-seq）和生物信息学分析进行预测，并通过qRT-PCR分析进一步证实。本研究表明，NF可通过将细胞周期阻滞在G2期对HCC细胞的增殖发挥抑制作用。此外，与对照组相比，NF可呈浓度依赖性增加凋亡细胞的比例。本研究证实，NF可抑制HCC细胞的增殖和细胞周期，同时加速凋亡，这被确定与HER2-AKT/ERK1/2信号通路的抑制密切相关。
