Sensitisation of human lung adenocarcinoma A549 cells to radiotherapy by Nimotuzumab is associated with enhanced apoptosis and cell cycle arrest in the G2/M phase

Cell Biol Int. 2015 Feb;39(2):146-51. doi: 10.1002/cbin.10342. Epub 2014 Jul 28.

Abstract

The epidermal growth factor receptor (EGFR) plays an important role in tumorigenesis and maintenance of cancers, making it a possible therapeutic target for cancer treatment. Nimotuzumab (h-R3), a humanised monoclonal antibody against EGFR, sensitises human lung adenocarcinoma A549 cells to radiotherapy. We have investigated the underlying molecular mechanism by treating A549 cells with Nimotuzumab (100 μg/mL) alone or in combination with a single dose of 2 Gy irradiation, and analysing apoptosis and cell cycle distribution by flow cytometry. Nimotuzumab significantly enhanced radiation-induced apoptosis of A549 cells as evidenced by increased cell apoptosis (7.15 ± 0.30%) compared with the control group (1.08 ± 0.25%), Nimotuzumab alone group (4.89 ± 0.30%) and irradiation alone group (5.90 ± 0.15%). Combining Nimotuzumab with irradiation significantly arrested cells in the G2/M phase (43. ± 0.36%) compared radiotherapy alone (18.7 ± 0.35%) and single Nimotuzumab treatment (27.2 ± 0.17%). A combination of Nimotuzumab with radiation increased apoptosis and G2/M phase arrest in human lung adenocarcinoma A549 cells, suggesting potential development of combinatorial therapy of Nimotuzumab with radiotherapy for lung cancer.

Keywords: apoptosis; cell cycle; lung adenocarcinoma cell line A549; nimotuzumab (h-R3); radiation therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma / radiotherapy
  • Adenocarcinoma of Lung
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / radiation effects
  • Cell Line, Tumor
  • ErbB Receptors / immunology
  • ErbB Receptors / metabolism
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • G2 Phase Cell Cycle Checkpoints / radiation effects
  • Gamma Rays
  • Humans
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / radiotherapy
  • M Phase Cell Cycle Checkpoints / drug effects
  • M Phase Cell Cycle Checkpoints / radiation effects

Substances

  • Antibodies, Monoclonal, Humanized
  • nimotuzumab
  • ErbB Receptors