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 human papillomavirus (HPV) is involved in causing cervical carcinoma. The HPV oncoproteins E6 and E7 immortalize human keratinocytes is mostly resulted from inactivation of tumor suppressor proteins p53 and pRB, which also play an important role in regulating the expression of pro- and antiangiogenic factors. The present study was conducted to determine whether IFN--inducible protein 10 (IP-10)/CXC chemokine ligand 10(CXCL10), one of the potent antiangiogenic chemokines, can inhibit the growth of cervical cancer. Plasmid DNA encoding CXCL10 was encapsulated with cationic liposomes, mice were treated with DNA-liposome mixture 6 times with the 5-day interval. Our results demonstrated that CXCL10 could reduce the level of HPV oncoproteins E6 and E7 in cervical cancer cells. In vivo study showed that CXCL10 could inhibit the growth of tumor in the immunodeficiency mice. Immunohistology analysis revealed that CXCL10 downregulated the microvessel density and the expression of PCNA in tumor tissues. TUNEL staining demonstrated CXCL10 significantly increase the apoptotic rate. Our data suggest that CXCL10 can inhibit the growth of cervical carcinoma through modulating the formation of microvessel and the expression of HPV oncoproteins E6 and E7. The present findings also provide further evidence of the anti-tumor effects of CXCL10, and may be of importance for the further exploration of the potential application of this molecule in the treatment of cervical carcinoma.
Wang
Ling-lin
LL
Chen
Ping
P
Luo
Shan
S
Li
Jie
J
Liu
Kang
K
Hu
Huo-zhen
HZ
Wei
Yu-quan
YQ
D020533:Angiogenesis Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009856:Oncogene Proteins, Viral / Q000032:analysis / Q000378:metabolism; D050725:Papillomavirus E7 Proteins / Q000032:analysis / Q000378:metabolism; D012097:Repressor Proteins / Q000032:analysis / Q000378:metabolism; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
D020533:Angiogenesis Inhibitors; D000998:Antiviral Agents; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16