Early downregulation of acute phase proteins after doxorubicin exposition in patients with breast cancer

Tumour Biol. 2016 Mar;37(3):3775-83. doi: 10.1007/s13277-015-4203-7. Epub 2015 Oct 15.

Abstract

Chemotherapy remains the first-choice option for adjuvant therapy in breast cancer. Here, we investigated the impact of the first chemotherapic cycle of doxorubicin on the plasmatic-proteomic profiling of women diagnosed with breast cancer (n = 87). Blood samples were obtained from the same patient before and after doxorubicin infusion (1 h, 60 mg/m(2)) and processed for label-free LC-MS proteomic screening. A total of 80 proteins were downregulated after chemotherapy. In silico analysis revealed that the main biological process enrolled was inflammation and canonical pathways involving acute phase proteins. TNF-α, IL-1β, IL-12, TGF-β1, clusterin, and gelsolin were chosen as relevant for further validation. All selected targets presented reduced plasmatic levels after treatment. Our results indicate that doxorubicin downregulated acute phase proteins immediately after its infusion. Since such proteins are cancer promoting, its downregulation could support the effectiveness of doxorubicin along treatment.

Keywords: Acute phase proteins; Breast cancer; Cytokines; Downregulation; Doxorubicin; Label-free proteomics.

MeSH terms

  • Acute-Phase Proteins / metabolism*
  • Adult
  • Aged
  • Antibiotics, Antineoplastic / administration & dosage
  • Antibiotics, Antineoplastic / therapeutic use
  • Blotting, Western
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Chromatography, Liquid
  • Computer Simulation
  • Down-Regulation*
  • Doxorubicin / administration & dosage
  • Doxorubicin / therapeutic use*
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Mass Spectrometry
  • Middle Aged
  • Proteome / drug effects
  • Proteome / metabolism
  • Proteomics / methods
  • Time Factors

Substances

  • Acute-Phase Proteins
  • Antibiotics, Antineoplastic
  • Proteome
  • Doxorubicin