Effects of doxorubicin and docetaxel on susceptibility to apoptosis in high expression level of survivin in HEK and HEK-S cell lines as in vitro models

Biochem Biophys Res Commun. 2020 Oct 29;532(1):139-144. doi: 10.1016/j.bbrc.2020.08.028. Epub 2020 Aug 20.

Abstract

A major problem in the cancer treatment is the inherent resistance to chemotherapy. Identifying proteins that, once introduced in cancer cells, lead to a decreased efficiency of treatment outcome constitutes a major goal for biomedical research and applications. Survivin is a protein of IAPs family which its high expression can be a potential candidate for regulating cell death and survival in cancer therapy. To investigate the association of survivin increment and resistance to drug, survivin-reconstituted HEK (HEK-S) and HEK cells were used as in vitro models for the doxorubicin and docetaxel cellular response. Both morphological observation and survival assay exhibited that survivin reconstitution cells were significantly resistant to apoptotic stimuli by both drugs. It was observed that survivin overexpression has led to a decrease in caspase 3/7 activity and ROS level of cells but an increase in ATP content. Also, survivin-reconstituted cell displayed less red fluorescence compared to control after stimulation by drugs. Moreover, wound healing assay showed the ability of survivin to cause neighbouring cells to increase resistance to induction. These findings demonstrated survivin could be a potential target that can be inhibited the function of different drugs with various mechanisms in chemotherapy.

Keywords: Apoptosis; Docetaxel; Doxorubicin; HEK-S; Survivin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Movement
  • Docetaxel / pharmacology*
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm
  • HEK293 Cells
  • Humans
  • Inhibitor of Apoptosis Proteins / metabolism
  • Models, Biological
  • Reactive Oxygen Species / metabolism
  • Survivin / metabolism*

Substances

  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • Reactive Oxygen Species
  • Survivin
  • Docetaxel
  • Doxorubicin
  • Adenosine Triphosphate
  • CASP3 protein, human
  • CASP7 protein, human
  • Caspase 3
  • Caspase 7