pRb-expressing adenovirus Ad5-Rb attenuates the p53-induced apoptosis in cervical cancer cell lines

Eur J Cancer. 2001 Dec;37(18):2475-83. doi: 10.1016/s0959-8049(01)00308-2.


The retinoblastoma protein (pRb), the gene product of the first reported tumour suppressor gene, is functionally inactivated by the E7 protein of high-risk human papillomavirus (HPV) found in most human cervical cancers. We have, in this study, constructed an adenoviral vector expressing wild-type pRb (Ad5-Rb) and used the constructed Ad5-Rb to transfect the osteosarcoma cell line Saos-2, and three cervical cancer cell lines HeLa, SiHa and C-33A. Our results showed that pRb caused G1 arrest in Saos-2 cells after transfection with Ad5-Rb. The number of colonies formed by the Ad5-Rb-transfected Saos-2 cells in soft agar was also found to be significantly lower (P<0.05) than those transfected with the adenoviral control expressing Escherichia coli beta-galactosidase (Ad5-LacZ). The transfection of Ad5-Rb caused an increase in the population of SiHa and C-33A cells in the G1 phase from 53.0 and 52.9% to 72.4 and 64.3%, respectively, but not in the HeLa cells. However, Ad5-Rb did not show any inhibitory effect on the growth of SiHa, HeLa and C-33A cells, and inhibition of colony formation in soft agar was not observed either. In contrast, flow cytometric analysis showed that Ad5-p53, a p53-expressing adenovirus, induced apoptosis, i.e. the appearance of sub-G1 peak, in all three tested cervical cancer cell lines. Nevertheless, the Ad5-p53-induced apoptosis was partially inhibited when Ad5-Rb was added simultaneously. These findings suggested that pRb may not be a good candidate for cervical cancer gene therapy. Our data also showed that the use of full-length pRb in combination with TP53 might not be a suitable strategy for cancer gene therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Apoptosis* / genetics
  • Cell Division / genetics
  • DNA, Neoplasm / analysis
  • Female
  • Flow Cytometry
  • Genes, p53 / genetics*
  • Genetic Vectors / genetics
  • Humans
  • Osteosarcoma / pathology*
  • Retinoblastoma Protein / genetics*
  • Transfection / methods
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / physiology
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / pathology*


  • DNA, Neoplasm
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53