Exploring the Effect of Polyphyllin I on Hepatitis B Virus-related Liver Cancer through Network Pharmacology and in

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Shuxian Yu1,2, Wenhui Gao1, Puhua Zeng2

  • 1School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha 410208, P.R. China.

Combinatorial Chemistry & High Throughput Screening
|August 16, 2021
PubMed
Abstract

Insights

Polyphyllin I (PPI) effectively inhibits HBV-related liver cancer by promoting cancer cell apoptosis. This study utilized network pharmacology and in vitro experiments to uncover PPI's therapeutic mechanism against liver cancer.

Area of Science:

  • Pharmacology
  • Oncology
  • Bioinformatics

Background:

  • Hepatocellular carcinoma (HCC) remains a significant global health challenge, particularly in cases linked to Hepatitis B Virus (HBV) infection.
  • Identifying novel therapeutic agents and understanding their mechanisms of action are crucial for improving HCC treatment outcomes.

Purpose of the Study:

  • To investigate the therapeutic effects of Polyphyllin I (PPI) on HBV-related liver cancer.
  • To elucidate the underlying mechanism of PPI action using network pharmacology and in vitro experimental validation.

Main Methods:

  • Network pharmacology was employed to predict Polyphyllin I (PPI) targets and analyze its interactions with liver cancer targets.
  • Molecular docking was performed to assess the binding affinity of PPI with key predicted targets.
  • In vitro experiments using HepG2 and HBV-transfected HepG2.2.15 liver cancer cells were conducted to evaluate PPI's effects on cell proliferation, metastasis, and apoptosis.

Main Results:

  • Network pharmacology identified 161 PPI targets, with 13 intersecting with liver cancer targets. Molecular docking revealed strong binding affinity between PPI and STAT3, PTP1B, IL2, and BCL2L1.
  • In vitro studies demonstrated that PPI significantly inhibited liver cancer cell proliferation and metastasis in a dose-dependent manner (P<0.01).
  • PPI treatment markedly promoted apoptosis in both HepG2 and HepG2.2.15 cells at concentrations of 1.5, 3, and 6 μmol/L (P<0.01).

Conclusions:

  • Polyphyllin I (PPI) exhibits significant anti-liver cancer activity against HBV-related cancer.
  • The mechanism involves the inhibition of cancer cell proliferation and promotion of apoptosis, validated through integrated network pharmacology and in vitro experiments.
Keywords:
Hepatitis B virus-related liver cancerPolyphyllin Iapoptosismolecular dockingnetwork pharmacologyprimary liver cancer

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