Regression of tumors by IFN-alpha electroporation gene therapy and analysis of the responsible genes by cDNA array.
The key to success with nonviral gene therapy as a treatment for cancer is to discover effective therapeutic genes and gene delivery methods and to understand how tumors are eradicated. We discovered that electroporation of IFN-alpha DNA into tumors in the SCCVII tumor-bearing mice led to tumor eradication in 50% of the mice and a more than two-fold increase in survival time when compared with controls (P = 0.0012). Analyses using cDNA array and Northern blot indicated that the genes responsible for the therapeutic effect of electro-IFN-alpha gene therapy included IRF-7, Granzyme A, Granzyme C, Gjb2, Krt14, Mig, IP-10 and MCP3. Because most of these genes have been known to either inhibit angiogenesis (Mig, IP-10), inhibit tumor growth (Gjb2, MCP3), kill tumor cells (Granzyme A and C), or induce expression of antitumor gene (IRF-7), they may become promising therapeutic gene candidates for a combination gene therapy approach to cancer treatment.
Li
S
S
Department of Otolaryngology/Head and Neck Surgery, Henry Ford Health System, Detroit, MI 48202, USA.
Xia
X
X
Zhang
X
X
Suen
J
J
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D054410:Chemokine CCL7; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000235:genetics; D000072259:Connexin 26; D017630:Connexins / Q000235:genetics; D016207:Cytokines; D004247:DNA / Q000008:administration & dosage*; D004268:DNA-Binding Proteins / Q000235:genetics; D018274:Electroporation / Q000379:methods*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D053804:Granzymes; D036341:Intercellular Signaling Peptides and Proteins; D050839:Interferon Regulatory Factor-7; D007371:Interferon-gamma / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D018945:Monocyte Chemoattractant Proteins / Q000235:genetics; D009374:Neoplasms, Experimental / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis; D011897:Random Allocation; D012697:Serine Endopeptidases / Q000235:genetics
C515450:CCL7 protein, human; C080810:CXCL9 protein, human; C515451:Ccl7 protein, mouse; D054410:Chemokine CCL7; D054357:Chemokine CXCL10; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D017630:Connexins; D016207:Cytokines; D004268:DNA-Binding Proteins; C000607042:GJB2 protein, human; C000607043:Gjb2 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse; D018945:Monocyte Chemoattractant Proteins; D000072259:Connexin 26; D007371:Interferon-gamma; D004247:DNA; D053804:Granzymes; C509216:Gzmc protein, mouse; D012697:Serine Endopeptidases; C509212:GZMA protein, human