The antineoplastic effects of nuciferine on hepatocellular carcinoma are associated with suppression of the HER2-AKT/ERK1/2 signaling pathway

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.