Acteoside suppresses hepatocellular carcinoma progression via modulation of macrophage migration inhibitory factor and mitogen-activated protein kinase proteins

This study investigated acteoside's (ACT) inhibition of hepatocellular carcinoma (HCC) progression via macrophage migration inhibitory factor (MIF) and MAPK signaling; immunohistochemistry and in situ hybridization assessed MIF/MAPK expression in HCC, cirrhotic, and normal tissues. The effects of ACT on HepG2 and Huh-7 cells were evaluated via CCK-8 assays, wound healing assays, and Transwell assays. Cell lines with MIF knockdown or overexpression were established to explore MIF's role. Western blotting analyzed autophagy, apoptosis, and metastasis-related proteins. A rat HCC model validated in vitro findings using PCR, immunohistochemistry, and Western blot analysis. The research results suggest that the expression of MIF and MAPK-related proteins is upregulated in HCC and cirrhotic tissues. ACT significantly suppressed HepG2 and Huh-7 cell proliferation, migration, and invasion. It downregulated MIF, p-ERK, N-cadherin, VEGF, and Bcl-2 while upregulating p-JNK, p-p38 MAPK, Beclin-1, LC3B, Bax, and E-cadherin. In vivo, ACT reduced MIF, p-ERK, Bcl-2, and MMP-2 expression and increased p-JNK and p-p38 MAPK levels. Based on the above results, this study concludes that the progression of HCC progression is associated with elevated MIF and MAPK activation. ACT suppresses HCC by modulating MIF and altering MAPK phosphorylation, promoting autophagy and apoptosis while inhibiting invasion and migration.