Potential Therapeutic Effect of Natural Killer Cells on Doxorubicin-Resistant Breast Cancer Cells In Vitro

PLoS One. 2015 Aug 21;10(8):e0136209. doi: 10.1371/journal.pone.0136209. eCollection 2015.

Abstract

Objective: The aim of this study was to explore the therapeutic effect of natural killer (NK) cells on human doxorubicin-sensitive and resistant breast adenocarcinoma.

Methods: Human doxorubicin-sensitive and resistant breast cancer cell lines (MCF-7 and MCF-7/ADR) were tagged with renilla luciferase (Rluc) (MCF-7/RC and MCF-7/ADR/RC). NK cells were tagged with enhanced firefly luciferase (effluc) using a recombinant retrovirus transfection (NKF). Expression of Rluc, effluc, and NK cell surface markers CD16, CD56 as well as death receptors, DR4 and DR5, were assessed by using flow cytometry. In vitro cytotoxic effect of NK to MCF-7 and MCF-7/ADR was measured and in vivo bioluminescence imaging was also performed to visualize MCF-7/RC, MCF-7/ADR, and NKF in an animal model.

Results: NK92-MI, MCF-7, and MCF-7/ADR cells were successfully labeled with Rluc or effluc. Both the target breast cancer cells (with Rluc) and therapeutic NK cells (with effluc) were noninvasively visualized in nude mice. Doxorubicin-resistant breast cancer cells (MCF-7/ADR) presented a higher expression of DR5 and were more sensitive to NK cells compared with doxorubicin-sensitive breast cancer cells (MCF-7).

Conclusion: The results of present study suggest that NK cell therapy has a therapeutic effect on doxorubicin-sensitive and resistant breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology*
  • Breast / drug effects
  • Breast / immunology
  • Breast / pathology*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell- and Tissue-Based Therapy
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Female
  • Humans
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / transplantation*
  • MCF-7 Cells
  • Mice, Inbred BALB C
  • Mice, Nude
  • Optical Imaging
  • Receptors, Death Domain / analysis
  • Receptors, Death Domain / immunology

Substances

  • Antibiotics, Antineoplastic
  • Receptors, Death Domain
  • Doxorubicin