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Updated: Oct 26, 2025

Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
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SIRT3-mediated mitochondrial unfolded protein response weakens breast cancer sensitivity to cisplatin

Hao Chen1, Dong-Ming Zhang1, Zhi-Ping Zhang1

  • 1Department of General Surgery, Baotou Central Hospital, No. 61, Huancheng Road, Donghe District, Baotou City, Inner Mongolia, China.

Genes & Genomics
|August 2, 2021
PubMed
Abstract

Insights

The mitochondrial unfolded protein response (UPRmt), regulated by SIRT3, protects breast cancer cells from cisplatin chemotherapy. Targeting SIRT3-induced UPRmt may enhance chemotherapy sensitivity.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Stress Response

Background:

  • The mitochondrial unfolded protein response (UPRmt) is implicated in breast cancer development.
  • The specific role of UPRmt in breast cancer sensitivity to cisplatin chemotherapy remains unclear.

Purpose of the Study:

  • To investigate the influence of UPRmt on breast cancer cell sensitivity to cisplatin treatment.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR)
  • Western blotting
  • Immunofluorescence
  • Cell Counting Kit-8 (CCK-8)
  • Colony formation assays
  • Transwell migration assays
  • TUNEL staining

Main Results:

  • Cisplatin treatment elevated UPRmt markers (CLPP, HSP60, LONP1) in MCF7 and MDA-MB-231 cells.
  • The UPRmt inducer Nicotinamide ribose (NR) enhanced proliferation and invasion of cisplatin-treated breast cancer cells.
  • SIRT3 was identified as an enhancer of UPRmt in breast cancer cells; SIRT3 silencing counteracted NR's effects.

Conclusions:

  • SIRT3-mediated UPRmt confers protection to breast cancer cells against cisplatin.
  • Modulating SIRT3-induced UPRmt presents a potential therapeutic strategy to improve breast cancer chemotherapy efficacy.
Keywords:
Breast cancerMitochondrial unfolded protein responseNicotinamide riboseSIRT3

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