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  11. Metal-polyphenol-network Coated R612f Nanoparticles Reduce Drug Resistance In Hepatocellular Carcinoma By Inhibiting Stress Granules

Metal-polyphenol-network coated R612F nanoparticles reduce drug resistance in hepatocellular carcinoma by inhibiting stress granules

Yue Zhou1,2, Tongjia Zhang1, Shujie Wang1

  • 1Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Peking University Health Science Center, Beijing, 100191, P. R. China.

Cell Death Discovery
|August 28, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Stress granules (SGs) promote hepatocellular carcinoma (HCC) drug resistance. Targeting p110α methylation with novel nanoparticles inhibits SG assembly, reducing HCC resistance and enhancing anti-tumor effects.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Nanomedicine

Background:

  • Stress granules (SGs) are cytoplasmic assemblies involved in cellular stress responses.
  • SGs contribute to the progression and drug resistance of hepatocellular carcinoma (HCC).

Purpose of the Study:

  • To investigate the role of p110α in SG formation in HCC.
  • To develop a novel therapeutic strategy targeting SGs to overcome sorafenib resistance in HCC.

Main Methods:

  • Investigated the mechanism of p110α in SG assembly, including its Arg-Gly (RG) motif and methylation by PRMT1.
  • Developed and utilized metal-polyphenol-network-coated R612F nanoparticles (MPN-R612F) for targeted delivery.
  • Assessed the efficacy of MPN-R612F in combination with sorafenib in HCC cells.

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Main Results:

  • p110α is essential for SG assembly in HCC.
  • PRMT1-mediated methylation of p110α inhibits its recruitment to SGs.
  • MPN-R612F nanoparticles maintain p110α hypermethylation, inhibiting SG assembly and reducing sorafenib resistance.
  • Combination therapy of MPN-R612F and sorafenib demonstrated enhanced HCC cell killing and anti-tumor effects.

Conclusions:

  • p110α is a key regulator of SG formation in HCC.
  • Targeting p110α methylation via MPN-R612F nanoparticles offers a promising strategy to overcome sorafenib resistance.
  • This approach provides a novel therapeutic perspective for HCC treatment by targeting SGs.