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

Yuan,Fang; Gao,Qian; Tang,Hailin; Shi,Jun; Zhou,Yiqun

doi:10.3892/mmr.2022.12638

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

Authors:
- Fang Yuan
- Qian Gao
- Hailin Tang
- Jun Shi
- Yiqun Zhou
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Affiliations: Department of Liver Disease, Suzhou Hospital of Integrated Traditional Chinese and Western Medicine, Suzhou, Jiangsu 215101, P.R. China
Published online on: February 11, 2022 https://doi.org/10.3892/mmr.2022.12638
Article Number: 122
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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