Related Experiment Video

Updated: Dec 17, 2025

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity
09:32

Drug-Induced Senescence in Liver Cells Promotes M2 Macrophage Polarization: Implications for Tyrosine Kinase Inhibitor-Associated Hepatotoxicity

Published on: October 17, 2025

295

Sirt3 promotes hepatocellular carcinoma cells sensitivity to regorafenib through the acceleration of mitochondrial

Ruobing Wang1, Yahui Liu1, Xuguang Mi2

  • 1Department of Hepatobiliary and Pancreatic Surgery, the First Hospital of Jilin University, Changchun, Jilin, 130021, China.

Archives of Biochemistry and Biophysics
|June 21, 2020
PubMed

Insights

Regorafenib causes mitochondrial dysfunction in liver cancer cells by inhibiting Sirt3. Overexpressing Sirt3 worsens this effect, increasing cell death and suggesting Sirt3 activators could enhance regorafenib treatment for hepatocellular carcinoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Regorafenib, a kinase inhibitor, is approved for advanced hepatocellular carcinoma (HCC).
  • Regorafenib induces mitochondrial toxicity, impairing mitochondrial function.
  • Sirtuin 3 (Sirt3) plays a role in regulating mitochondrial function in cancer.

Purpose of the Study:

  • To investigate Sirt3's role in regorafenib-induced mitochondrial dysfunction in liver cancer cells.
  • To explore the mechanism by which Sirt3 influences hepatocellular carcinoma cell response to regorafenib.

Main Methods:

  • Dose-dependent analysis of regorafenib effects on Sirt3 and p-ERK expression.
  • Bioinformatic analysis of Sirt3 expression in liver cancer tissues and correlation with overall survival.
  • Sirt3 overexpression studies using plasmid transfection.
  • Assays for apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and cellular oxygen consumption.

Main Results:

  • Regorafenib inhibited Sirt3 and p-ERK expression in HCC cells.
  • Low Sirt3 expression correlated with worse overall survival in liver cancer patients.
  • Sirt3 overexpression sensitized HCC cells to regorafenib, increasing apoptosis and ROS levels.
  • Sirt3 overexpression accelerated mitochondrial depolarization and impaired the electron transport chain, leading to mitochondrial dysfunction.

Conclusions:

  • Sirt3 overexpression exacerbates regorafenib-induced mitochondrial dysfunction, ROS production, and apoptosis in liver cancer cells.
  • Sirt3 plays a critical role in the cellular response to regorafenib treatment.
  • Combining regorafenib with Sirt3 activators may represent a novel therapeutic strategy for HCC.
Keywords:
Liver cancerMitochondriaRegorafenibSirt3

More Related Videos

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment11:13

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

2.1K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.5K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.1K
Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are...
4.1K