Antitumor efficacy of combination of interferon-gamma-inducible protein 10 gene with gemcitabine, a study in murine model.
BACKGROUND
Interferon-gamma-inducible protein 10 (IP-10) is a potent inhibitor of tumor angiogenesis. It has been reported that the antiangiogenic therapy combined with chemotherapy has synergistic effects.


METHODS
To elucidate the mechanisms of IP-10 gene combined with a chemotherapy agent, we intramuscularly injected pBLAST-IP-10 expression plasmid combined with gemcitabine into tumor-bearing mice.


RESULTS
The proliferation of endothelial cells was effectively inhibited by IP-10 combined with gemcitabine in vitro. Treatment with pBLAST-IP-10 twice a week for 4 weeks combined with gemcitabine 10 mg/kg (once a week) resulted in sustained high level of IP-10 protein in serum, inhibition of tumor growth and prolongation of the survival of tumor-bearing mice. Compared with administration of IP-10 plasmid or gemcitabine alone, the angiogenesis in tumors were apparently inhibited, and the numbers of apoptotic cells and lymphocytes in tumor increased in the combination therapy group.


CONCLUSIONS
Our data indicate that the gene therapy of antiangiogenesis by intramuscular delivery of plasmid DNA encoding IP-10 combined with gemcitabine has synergistic effects on tumor by inhibiting the proliferation of endothelial cells, inducing the apoptosis of tumor cells, and recruiting lymphocytes to tumor in murine models. The present findings provided evidence of antitumor effects of genetherapy combined with chemotherapy.
Mei
Kai
K
1Department of Oncology, Sichuan Cancer Hospital, Chengdu, 610041, PR China. meikai1973@yahoo.com.cn
Wang
Lian
L
Tian
Ling
L
Yu
Jingrui
J
Zhang
Zhixuan
Z
Wei
Yuquan
Y
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D017209:Apoptosis; D019556:COS Cells; D054357:Chemokine CXCL10 / Q000235:genetics* / Q000378:metabolism; D002522:Chlorocebus aethiops; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015316:Genetic Therapy; D051379:Mice; D023421:Models, Animal; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000628:therapy*; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D000093542:Gemcitabine
D020533:Angiogenesis Inhibitors; D000964:Antimetabolites, Antineoplastic; D054357:Chemokine CXCL10; D003841:Deoxycytidine; D000093542:Gemcitabine