Related Experiment Video

Updated: Aug 12, 2025

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

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Regorafenib induces Bim-mediated intrinsic apoptosis by blocking AKT-mediated FOXO3a nuclear export

Beini Sun1, Hongce Chen1, Xiaoping Wang2

  • 1MOE Key Laboratory of Laser Life Science & Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.

Cell Death Discovery
|January 31, 2023
PubMed

Insights

Regorafenib triggers cancer cell death by activating the intrinsic apoptosis pathway. This multi-kinase inhibitor deactivates PI3K/AKT signaling, promoting FOXO3a nuclear localization and Bim expression, leading to apoptosis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Pharmacology

Background:

  • Regorafenib (REGO) is an oral multi-kinase inhibitor with demonstrated antitumor efficacy.
  • Understanding the precise molecular mechanisms of REGO-induced apoptosis is crucial for optimizing its therapeutic application.

Purpose of the Study:

  • To elucidate the molecular pathways through which Regorafenib induces apoptosis in cancer cells.
  • To investigate the role of the PI3K/AKT/FOXO3a signaling axis in REGO's mechanism of action.

Main Methods:

  • Cell viability, proliferation, and migration assays were performed.
  • Western blotting was used to assess protein levels (PI3K, p-AKT, FOXO3a, Bim, Bax, Bak).
  • Reactive oxygen species (ROS) production, nuclear condensation, and mitochondrial translocation of proteins were analyzed. Fluorescence resonance energy transfer (FRET) was employed.

Main Results:

  • Regorafenib induced cancer cell apoptosis, inhibited proliferation and migration, and increased ROS production.
  • REGO deactivated the PI3K/AKT pathway, leading to FOXO3a nuclear localization and subsequent Bim upregulation.
  • Bim translocation to mitochondria and subsequent Bax/Bak activation were critical for REGO-induced apoptosis.

Conclusions:

  • Regorafenib promotes apoptosis through the PI3K/AKT/FOXO3a/Bim-mediated intrinsic pathway.
  • The study highlights the central role of Bim in mediating REGO's cytotoxic effects via mitochondrial pathways.
  • Targeting this pathway could offer new therapeutic strategies for cancer treatment.

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