Quantitative proteomics analysis of differentially expressed proteins induced by astragaloside IV in cervical cancer cell invasion

Cell Mol Biol Lett. 2020 Mar 31:25:25. doi: 10.1186/s11658-020-00218-9. eCollection 2020.

Abstract

Background: Cervical cancer remains the second leading cause of mortality in women in developing countries. While surgery, chemotherapy, radiotherapy, and vaccine therapy are being applied for its treatment, individually or in combination, the survival rate in advanced cervical cancer patients is still very low. Traditional Chinese medicine has been found to be effective in the treatment of cervical cancer. Astragaloside IV (AS-IV), a compound belonging to Astragalus polysaccharides, shows anticancer activity through several cell signaling pathways. However, the detailed molecular mechanism governing the anticancer activity of AS-IV remains unknown.

Material and methods: In our study, we performed tumor xenograft analysis, transwell cell migration and invasion assay, Western blot analysis, and iTRAQ combination by parallel reaction monitoring (PRM) analysis to study the molecular mechanism of AS-IV in the suppression of cervical cancer cell invasion.

Results: Our results showed that AS-IV suppressed cervical cancer cell invasion and induced autophagy in them, with the tumor growth curve increasing slowly. We also identified 32 proteins that were differentially expressed in the SiHa cells when treated with AS-IV, with 16 of them involved in the upregulation and 16 in the downregulation of these cells. These differentially expressed proteins, which were predominantly actin-myosin complexes, controlled cell proliferation and cell development by steroid binding and altering the composition of the cell cytoskeleton. DCP1A and TMSB4X, the two proteins regulating autophagy, increased in cervical cancer cells when treated with AS-IV.

Conclusions: We conclude that AS-IV could inhibit cervical cancer invasion by inducing autophagy in cervical cancer cells. Since iTRAQ combination by PRM has been observed to be useful in identifying macromolecular target compounds, it may be considered as a novel strategy in the screening of anticancer compounds used in the treatment of cervical cancer.

Keywords: Astragaloside IV; Cervical cancer; Parallel reaction monitoring; Quantitative proteomics; iTRAQ.

MeSH terms

  • Animals
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Drugs, Chinese Herbal / pharmacology*
  • Endoribonucleases / metabolism
  • Female
  • Gene Ontology
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Protein Interaction Maps / drug effects
  • Proteome / drug effects*
  • Proteomics
  • Saponins / administration & dosage
  • Saponins / pharmacology*
  • Signal Transduction / drug effects*
  • Thymosin / metabolism
  • Trans-Activators / metabolism
  • Triterpenes / administration & dosage
  • Triterpenes / pharmacology*
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • Drugs, Chinese Herbal
  • Proteome
  • Saponins
  • Trans-Activators
  • Triterpenes
  • astragaloside A
  • Thymosin
  • Endoribonucleases
  • DCP1A protein, human