E1A inhibits the proliferation of human cervical cancer cells (HeLa cells) by apoptosis induction through activation of HER-2/Neu/Caspase-3 pathway

Med Oncol. 2008;25(2):222-8. doi: 10.1007/s12032-007-9007-1. Epub 2007 Sep 28.


Objective: This study is to investigate the inhibitory effect of E1A gene on the cell proliferation of HeLa cells and its mechanism related to apoptosis.

Methods: MTT assay and soft agar colony formation assay were employed to justify the inhibition activity of E1A on the proliferation of HeLa cells transfected with E1A gene. Western Blot, RT-PCR and Real-time quantitative RT-PCR were used to detect the gene expression of E1A, HER-2/Neu and Caspase-3 in HeLa cells, respectively. The Caspase-3 activity was monitored by ApoAlert Caspase-3 Assay. The redistribution of cell cycles and apoptosis of HeLa cells regulated by E1A expression were evaluated by flow cytometry.

Results: E1A expression significantly inhibits the cell proliferation and anchorage-independent cell growth of HeLa, with the respective highest inhibition rate of 40.7% and 43.4% (P < 0.01). HER-2/Neu expression in HeLa was significantly down-regulated by E1A, while the protein expression and activity of Caspase-3 was up-regulated by E1A expression. Flow cytometry revealed that E1A transfection in HeLa increased the cell number at G1 stage and simultaneously decreased the cell number at S stage. E1A transfection induced 8.71% of HeLa cells at apoptosis status.

Conclusions: E1A significantly inhibits the cell proliferation of HeLa by the apoptosis induction through HER-2/Neu/Caspase-3 pathway. These results encourage us to continue an in-vivo study and preclinical development of LPD-E1A as a novel gene therapeutic agent for human cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenovirus E1A Proteins / analysis
  • Adenovirus E1A Proteins / genetics*
  • Apoptosis*
  • Caspase 3 / physiology*
  • Cell Proliferation
  • Enzyme Activation
  • Female
  • Genetic Therapy*
  • HeLa Cells
  • Humans
  • RNA, Messenger / analysis
  • Receptor, ErbB-2 / physiology*
  • Uterine Cervical Neoplasms / therapy*


  • Adenovirus E1A Proteins
  • RNA, Messenger
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Caspase 3