Multi-omics reveal inhibitory effects of Protopanaxadiol on metastasis through PI3K-Akt and MAPK pathway in human cervical cancer HeLa cells

Women are more prone to develop a risk of cervical cancer (CC), a cancer with a high metastatic rate and unfavorable prognoses. Novel natural therapeutic agents are urgently needed to potentially prevent the metastasis. This study has demonstrated the molecular processes underlying effect of protopanaxadiol (PPD) (molecule produced from ginseng) on HeLa cell metastasis. The results of colony formation assays showed a notable reduction in colony formation that was dose-dependent, peaking at 35 mu M PPD. 5477 differentially expressed genes (DEGs) and 97 differentially expressed microRNAs (DEMs) were found using miRNA-seq and transcriptome analysis; these results were confirmed by RT-PCR. Relationships between these miRNAs and signaling pathways, specifically the PI3K-Akt and MAPK pathways, were revealed by bioinformatics research. Functional experiments verified that PPD inhibits cell metastasis by upregulating E-cadherin expression and downregulating MMP-2, MMP-9, N-cadherin, and vimentin expression levels. Furthermore, as indicated by lower levels of p-PI3K and p-AKT, PPD downregulated the RAS/MEK/ERK, p38 MAPK, and PI3K/AKT pathways. It was confirmed using the AKT activator SC79 that the PI3K/Akt pathway mediates the effects of PPD on migration. Overall, PPD efficiently blocked the advancement of CC through targeting the PI3K/Akt signaling pathway, offering a possible treatment strategy.