Elevated survivin mediated multidrug resistance and reduced apoptosis in breast cancer stem cells

J BUON. 2015 Sep-Oct;20(5):1287-94.

Abstract

Purpose: Overexpression of survivin in breast cancer cells is associated with aberrant inhibition of apoptosis which leads to massive proliferation of cancer cells. Downregulation of survivin by the anticancer agent prodigiosin can efficiently induce apoptosis in cancer cells.

Methods: The levels of survivin expression in breast cancer stem like side population (SP) cells were assessed. Analyzed were also the rate of apoptosis, drug resistance and the efficiency of clone formation of breast cancer SP cells after treatment with progiosin.

Results: Breast cancer samples contained about 2.7% of cancer stem like SP cells which possessed elevated mRNA expression of stem cell proteins Oct-4, EpCAM and ABC transporter ABCG2, essential for the maintenance of SP cells. Furthermore, the SP cells displayed overexpression of survivin in conjunction with reduced apoptosis and increased multidrug resistance. After treatment with prodigiosin, the SP cells became more sensitive to apoptosis and to several chemotherapeutic agents.

Conclusion: These data suggest that increased expression of survivin in SP cells is one of the major factors involved in apoptosis and resistance to chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apoptosis*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology*
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Inhibitor of Apoptosis Proteins / physiology*
  • Middle Aged
  • Neoplastic Stem Cells / pathology*
  • Survivin

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Survivin