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

摘要

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-y-inducible protein 10/CXCL1O (CXC chemokine ligand 10), one of the potent antiangiogenic chemokines, can inhibit the growth of cervical cancer. Plasmid DNA encoding CXCL1O was encapsulated with cationic liposomes, and mice were tre_ated with a DNA/liposome mixture six times at 5-day intervals. Our results demonstrated that CXCL1O could reduce the level of the HPV oncoproteins E6 and E7 in cervical-cancer cells. In vivo study showed that CXCL1O could inhibit the growth of tumour in the immunodeficient mice. Immunohistology analysis revealed that CXCL1O down-regulated the mi_rovessel density and the expression of proliferating-cell nuclear antigen in tumour tissues. TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) staining demonstrated that CXCL1O significantly increases the apoptotic rate. Our results suggest that CXCL10 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 CXCL1O and may be of importance for further exploring the potential application of this molecule in the treatment of cervical carcinoma.