Related Experiment Video

Updated: May 8, 2026

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel
06:44

Generation of Prostate Cancer Cell Models of Resistance to the Anti-mitotic Agent Docetaxel

Published on: September 8, 2017

Nuclear Factor Erythroid 2-Related Factor 2 Negatively Regulates Docetaxel-Induced Ferroptosis in

Chunjin Ke1,2, Jiahua Gan3,4, Zilong Guo5

  • 1Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The World Journal of Men'S Health
|May 7, 2026
PubMed
Abstract

Insights

Docetaxel (DTX) triggers ferroptosis in castration-resistant prostate cancer (CRPC) cells, a process negatively regulated by nuclear factor erythroid 2-related factor 2 (NRF2). Combining DTX with TFRC-CAR-T cells enhances anti-tumor effects and cytokine secretion.

Area of Science:

  • Oncology
  • Cancer Cell Biology
  • Immunotherapy

Background:

  • Castration-resistant prostate cancer (CRPC) remains a significant clinical challenge.
  • Docetaxel (DTX) is a standard chemotherapy agent for CRPC.
  • Understanding novel mechanisms of DTX action and combination therapies is crucial.

Purpose of the Study:

  • To investigate if DTX induces ferroptosis in CRPC cells.
  • To elucidate the mechanism of DTX-induced ferroptosis, focusing on the role of NRF2.
  • To evaluate the combined anti-tumor efficacy and immune regulation of DTX with TFRC-CAR-T cells.

Main Methods:

  • DTX treatment of CRPC cells, assessing morphological, metabolic, and protein changes indicative of ferroptosis.
  • Transcriptome sequencing and gene set enrichment analysis to identify key regulatory pathways, including NRF2.
  • Silencing NRF2 (si-NRF2) to confirm its role in ferroptosis.
  • Construction and evaluation of TFRC-CAR-T cells combined with DTX for anti-tumor activity.

Main Results:

  • DTX induced ferroptosis in CRPC cells, evidenced by characteristic morphological and biochemical changes, partially reversed by ferroptosis inhibitors.
  • NRF2 was identified as a key negative regulator of DTX-induced ferroptosis.
  • Silencing NRF2 enhanced ferroptosis sensitivity.
  • Combined DTX and TFRC-CAR-T cells exhibited superior tumor killing and increased cytokine secretion compared to DTX alone.

Conclusions:

  • DTX effectively induces ferroptosis in CRPC cells, with NRF2 negatively regulating this process.
  • The combination of DTX and TFRC-CAR-T cells demonstrates enhanced anti-cancer efficacy and immunomodulatory effects in CRPC.
  • This combination therapy holds promise for improving treatment outcomes in CRPC.
Keywords:
DocetaxelFerroptosisNF-E2-related factor 2Prostatic neoplasms, castration-resistantReceptors, transferrin

Related Concept Videos

Necrosis01:16

Necrosis

Necrosis is considered as an “accidental” or unexpected form of cell death that ends in cell lysis. The first noticeable mention of “necrosis” was in 1859 when Rudolf Virchow used this term to describe advanced tissue breakdown in his compilation titled “Cell Pathology”.
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...