AAV-HGFK1 and Ad-p53 cocktail therapy prolongs survival of mice with colon cancer.
This study tried to evaluate the application of a novel cancer gene therapy using recombinant adeno-associated virus (AAV) carrying the kringle 1 domain of human hepatocyte growth factor (AAV-HGFK1) in combination with recombinant adenovirus carrying p53 gene (Ad-p53). BALB/c and nude mice models of colon cancer were established and the mice were treated with AAV-HGFK1 alone or in combination with Ad-p53. Combination of AAV-HGFK1 and Ad-p53 significantly prolonged the survival of the mice and also significantly inhibited primary and secondary tumor growth. Histochemical examination of the tumors revealed that AAV-HGFK1+Ad-p53 combinatorial treatment not only induced necrosis and apoptosis in the tumors but also suppressed tumor angiogenesis. The antiangiogenesis effect could likely be attributed to the ability of AAV-HGFK1+Ad-p53 viral cocktail to inhibit endothelial cell migration and proliferation. AAV-HGFK1+Ad-p53 also inhibited tumor cell growth in vitro by inhibiting epidermal growth factor receptor phosphorylation. Therefore, AAV-HGFK1+Ad-p53 cocktail therapy has a significantly higher therapeutic effect than AAV-HGFK1 or Ad-p53 alone and is a novel promising gene therapy for colon cancer.
Nie
Biao
B
Institute for Digestive Medicine and Department of Gastroenterology, Nanfang Hospital, Nanfang Medical University, Guangzhou, Republic of China.
Shen
Zan
Z
Wen
Jun-Bao
JB
Wong
Oscar Gee-Wan
OG
Hsueh
Wayne D
WD
Huo
Long-Fei
LF
Kung
Hsiang-Fu
HF
Jiang
Bo
B
Lin
Marie C M
MC
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000098:blood supply / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D000229:Dependovirus / Q000235:genetics*; D042783:Endothelial Cells / Q000473:pathology; D005260:Female; D015316:Genetic Therapy; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000473:pathology; D016019:Survival Analysis; D014161:Transduction, Genetic; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
C066855:HGF protein, human; D016159:Tumor Suppressor Protein p53; D017228:Hepatocyte Growth Factor