Anticancer Effects of Wild Baicalin on Hepatocellular Carcinoma: Downregulation of AKR1B10 and PI3K/AKT Signaling Pathways

Longjun Sun,1,* Wenjuan Chen,2,* Peixi Zhao,3 Bin Zhao,4 Guangyan Lei,1 Le Han,1,* Yili Zhang2,* 1Department of Thoracic Surgery, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 2Department of Oncology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 3Department of Department of Pharmacy, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 4Department of Epidemiology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Le Han, Department of Thoracic Surgery, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China, Email millyhan1@sohu.com Yili Zhang, Department of Oncology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China, Email doctor_z2023@stu.xjtu.edu.cnIntroduction: Hepatocellular carcinoma (HCC) is a common and deadly malignancy. Traditional Chinese medicine, such as the compound Astragalus (wild Baicalin), has shown promise in improving outcomes for HCC patients. This study aimed to investigate the effects of wild Baicalin on the human hepatoma cell line HepG2 and elucidate the underlying mechanisms, particularly the role of the AKR1B10 and PI3K/AKT signaling pathways.Methods: HepG2 cells were treated with varying concentrations of wild Baicalin. Cell proliferation, apoptosis, migration, invasion, and cell cycle were evaluated using CCK-8, flow cytometry, scratch, Transwell, and clonogenic assays, respectively. Transcriptome sequencing was performed to analyze gene expression changes induced by wild Baicalin. Differentially expressed genes were identified and analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The expression of AKR1B10 and PI3K was validated by qPCR.Results: Wild Baicalin inhibited HepG2 cell proliferation, induced apoptosis, suppressed migration and invasion, and caused cell cycle arrest in a dose-dependent manner. Transcriptome sequencing revealed 1202 differentially expressed genes, including 486 upregulated and 716 downregulated genes. GO analysis indicated that biological processes were pivotal in the anticancer mechanism of wild Baicalin, while KEGG analysis identified metabolic pathways as the most significantly regulated. AKR1B10 and PI3K, key genes in metabolic pathways, were downregulated by wild Baicalin, which was confirmed by qPCR.Discussion: The findings suggest that wild Baicalin exhibits potent anticancer effects against HepG2 cells by inducing apoptosis, inhibiting proliferation, migration, and invasion, and causing cell cycle arrest. The regulatory effects of wild Baicalin on the AKR1B10 and PI3K/AKT signaling pathways appear to be critical for its inhibitory effects on HCC cell proliferation. These results provide new insights into the mechanism of action of wild Baicalin and support its potential as a therapeutic approach for HCC treatment. Keywords: hepatocellular carcinoma, wild baicalin, transcriptome sequencing, apoptosis