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Dual function of programmed cell death 10 (PDCD10) in drug resistance

Cagri Urfali-Mamatoglu1, Hasan Hüseyin Kazan1, Ufuk Gündüz1

  • 1Department of Biological Sciences, Middle East Technical University, Ankara, Turkey.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|February 27, 2018
PubMed

Insights

Programmed Cell Death 10 (PDCD10) plays a dual role in cancer drug resistance. Modulating PDCD10 levels can either increase or decrease resistance, offering a novel target for overcoming chemotherapy challenges.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Death Research

Background:

  • Drug resistance is a significant hurdle in cancer chemotherapy, often involving altered apoptosis pathways.
  • Programmed Cell Death 10 (PDCD10) is implicated in cell survival and apoptosis, but its specific role in drug resistance remains unclear.

Purpose of the Study:

  • To investigate the role of PDCD10 in mediating resistance to anti-cancer agents across various cell lines.
  • To explore PDCD10 as a potential therapeutic target for reversing drug resistance in cancer.

Main Methods:

  • Analysis of PDCD10 expression in drug-resistant versus parental cancer cell lines (MCF7, HeLa).
  • Manipulation of PDCD10 levels using siRNA (down-regulation) and overexpression.
  • Assessment of apoptosis markers, including caspase 3/7 activity and related gene expression.

Main Results:

  • PDCD10 expression is cell- and drug-specific, showing down-regulation in doxorubicin/docetaxel-resistant MCF7 cells and up-regulation in doxorubicin-resistant HeLa cells.
  • Altering PDCD10 levels demonstrated a dual effect: down-regulation increased resistance in MCF7 cells, while it enhanced sensitivity in resistant HeLa cells. Overexpression showed converse effects.
  • Changes in PDCD10 expression correlated with altered caspase 3/7 activity and apoptosis-related gene expression.

Conclusions:

  • PDCD10 exhibits a novel dual role in cancer drug resistance, influencing sensitivity and resistance depending on the cellular context and drug.
  • Targeting PDCD10 presents a promising strategy for developing new therapies to overcome drug resistance in cancer treatment.
Keywords:
ApoptosisChemoresistancePDCD10Programmed cell death

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