Sensitization of rhTRAIL-resistant Triple-negative Breast Carcinoma Through Silibinin Co-Treatment

Anticancer Res. 2017 Dec;37(12):6593-6599. doi: 10.21873/anticanres.12116.

Abstract

Background/aim: Triple-negative breast cancer (TNBC) is the most fatal form of breast cancer due to the shortcomings of therapies. However, recombinant human tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) is a promising anticancer therapeutic that possesses the capability to promote the induction of apoptosis in cancer cells, but some TNBCs are resistant to rhTRAIL's pro-apoptotic effects. Therefore, a combinatorial treatment approach with silibinin and rhTRAIL was considered in order to sensitize rhTRAIL-resistant TNBCs.

Materials and methods: The co-treatment of rhTRAIL and silibinin's impact on apoptosis induction in rhTRAIL-resistant TNBC BT-20 and HCC1937 cells was inspected via application of Annexin V/PI assays and western blot analysis.

Results: Silibinin possessed the ability to sensitize the examined rhTRAIL-resistant TNBC cells to rhTRAIL-induced apoptosis through the up-regulation of death receptors 4 and 5 and the down-regulation of survivin transcriptionally.

Conclusion: Silibinin is a good sensitizing agent for rhTRAIL-resistant TNBCs.

Keywords: Apoptosis; breast cancer; death receptors; rhTRAIL; silibinin; survivin.

MeSH terms

  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Blotting, Western
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Resistance, Neoplasm / genetics
  • Drug Synergism
  • Female
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / genetics
  • Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
  • Recombinant Proteins / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Silybin
  • Silymarin / pharmacology*
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand / genetics
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Recombinant Proteins
  • Silymarin
  • Survivin
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10B protein, human
  • Silybin