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SPARC regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma

Hong-Wei Hua1,2,1, Hao-Sheng Jiang2,1, Ling Jia2

  • 1Oncology Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cancer Biomarkers : Section a of Disease Markers
|April 12, 2021
PubMed
Abstract

Insights

Secreted protein acidic and rich in cysteine (SPARC) regulates ferroptosis in hepatocellular carcinoma (HCC) cells, impacting sorafenib sensitivity. SPARC influences cell viability and oxidative stress, offering new insights into HCC treatment strategies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Secreted protein acidic and rich in cysteine (SPARC) is linked to cancer progression.
  • The precise role of SPARC in hepatocellular carcinoma (HCC) cell sensitivity to sorafenib and its underlying mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the role of SPARC in regulating sorafenib sensitivity in HCC cells.
  • To elucidate the molecular mechanisms, particularly ferroptosis, through which SPARC influences HCC cell response to sorafenib.

Main Methods:

  • Utilized human HCC cell lines (Hep3B and HepG2) treated with sorafenib, alone or with ferroptosis modulators.
  • Assessed cell viability, reactive oxygen species (ROS) production, lactate dehydrogenase (LDH) release, and protein expression via western blot.

Main Results:

  • SPARC overexpression enhanced sorafenib's cytotoxic effect and induced LDH release and ROS production.
  • SPARC depletion reduced sorafenib's efficacy and suppressed LDH release and ROS.
  • Ferroptosis activation promoted LDH release and ROS, while inhibition suppressed them, correlating with ferroptosis-related protein expression.

Conclusions:

  • SPARC plays a crucial role in regulating ferroptosis in HCC cells.
  • SPARC modulates HCC cell response to sorafenib through mechanisms involving ferroptosis and oxidative stress.
  • Findings enhance understanding of ferroptosis's molecular mechanisms in HCC and its regulation by SPARC in response to sorafenib.
Keywords:
Hepatocellular carcinomaSPARCferroptosissorafenib

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