Ophiopogonin-B targets PTP1B to inhibit the malignant progression of hepatocellular carcinoma by regulating the PI3K/AKT and AMPK signaling pathways

Ophiopogonin-B (OP-B) is a bioactive component from the root of Ophiopogon japonicus, which can exert anticancer effects on multiple malignant tumors. The present study aimed to uncover the effects of OP-B on hepatocellular carcinoma (HCC) and the underlying mechanisms. An HCC-xenografted mouse model was established and subsequently treated with OP-B (15 and 75 mg/kg) to observe the effects of OP-B on HCC progression and protein tyrosine phosphatase 1B (PTP1B) expression in vivo. The HCC cell line MHCC97-H was transfected with either PTP1B overexpression (Ov)-PTP1B or empty vector control, and then exposed to different concentrations of OP-B. Subsequently, PTP1B expression, cell viability, proliferation, apoptosis, migration, invasion and angiogenesis were evaluated by western blotting, reverse transcription-quantitative PCR, Cell Counting Kit-8, colony formation, TUNEL staining, wound healing, Transwell and tube formation assays. The expression of phosphatidylinositol 3 kinase (PI3K)/AKT and adenosine 5′-monophosphate-activated protein kinase (AMPK) was also assessed by western blot assay. The results showed that OP-B inhibited tumor growth and the expression of Ki67, CD31, VEGFA and PTP1B in HCC xenograft model. The expression of PTP1B in HCC cells was also inhibited by OP-B in a concentration-dependent manner. Results from the in vitro studies revealed that OP-B suppressed cell proliferation, migration, invasion and angiogenesis, and promoted apoptosis of HCC cells. However, PTP1B overexpression reversed the effect of OP-B on HCC cells. PI3K/AKT was inactivated and AMPK was activated by OP-B exposure in HCC cells, and PTP1B overexpression blocked these effects. In conclusion, OP-B effectively inhibited the progression of HCC both in vivo and in vitro. These effects may depend on downregulating PTP1B expression, thereby inactivating the PI3K/AKT pathway and activating the AMPK pathway.