CXC-chemokine-ligand-10 gene therapy efficiently inhibits the growth of cervical carcinoma on the basis of its anti-angiogenic and antiviral activity

Epidemiological studies have demonstrated that high-risk HPV (human papillomavirus) is involved in the development of cervical carcinoma. The HPV oncoproteins E6 and E7 in immortalized human keratinocytes mostly result from inactivation of the tumour-suppressor proteins p53 and pRb (retinoblastoma protein), which also play an important role in regulating the expression of pro- and anti-angiogenic factors. The present study was conducted to determine whether interferon-gamma-inducible protein 10/CXCL10 (CXC chemokine ligand 10), one of the potent anti-angiogenic chemokines, can inhibit the growth of cervical cancer. Plasmid DNA encoding CXCL 10 was encapsulated with cationic liposomes, and mice were treated with a DNA/liposome mixture six times at 5-day intervals. Our results demonstrated that CXCL10 could reduce the level of the HPV oncoproteins E6 and E7 in cervical-cancer cells. In vivo study showed that CXCL10 could inhibit the growth of tumour in the immunodeficient mice. Immunohistology analysis revealed that CXCL 10 down-regulated the microvessel density and the expression of proliferating-cell nuclear antigen in tumour tissues. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) staining demonstrated that CXCL10 significantly increases the apoptotic rate. Our results suggest that CXCL 10 can inhibit the growth of cervical carcinoma through modulating the formation of microvessels and the expression of the HPV oncoproteins E6 and E7. The present findings also provide further evidence of the antitumour effects of CXCL 10 and may be of importance for further exploring the potential application of this molecule in the treatment of cervical carcinoma.