Related Experiment Video
Updated: May 8, 2026
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
Summary
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.
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