Growth suppression of human laryngeal squamous cell carcinoma by adenovirus-mediated tissue factor pathway inhibitor gene 2.
OBJECTIVE
The purpose of this study was to explore the inhibiting role of adenoviral-mediated (Ad)-tissue factor pathway inhibitor (TFPI)-2 gene in the growth of laryngeal squamous cell carcinoma (LSCC).


METHODS
The nude mice bearing LSCC were prepared by intracutaneous injection of Hep-2 cell. Gene therapy was performed by injecting adenoviruses carrying TFPI-2 gene around tumors in the animal model.


METHODS
Eighteen nude mice bearing Hep-2 cell tumor were randomly separated into the treated group and control group. The former were injected with recombinant adenovirus Ad-TFPI-2 around the tumor, and the later were injected with equivalent Ad-LacZ. After treatment, differences of tumor weight, volume, and ultrastructure of tumor cells between these two groups were observed by measuring and using transmission electron microscope. Apoptosis in Hep-2 xenotransplants was detected using the terminal deoxy-transferase-mediated dUTP nick end labeling. In addition, the expressions of TFPI-2 protein and proliferating cell nuclear antigen (PCNA) in tumor tissues were detected using Western blot and immunohistochemistry, respectively.


RESULTS
The average weight and volume of tumor in the treated group were significantly lower than that in the control group (P < .01). The PCNA index was obviously lower in the tumors treated group than that in the control group (P < .01). In addition, cell apoptosis was observed in xenotransplants of the treated group but not in the control group.


CONCLUSIONS
Peritumor injection of Ad-TFPI-2 can inhibit growth of LSCC in nude mice model, and TFPI-2 might be a desirable gene for gene therapy in LSCC.
Department of Otorhinolaryngology--Head and Neck Surgery, The Second Affiliated Hospital, Harbin Medical University, Harbin, People's Republic of China.
Yanan
Y
Sun
Minqiang
M
Xie
Ming
M
Liu
Dejun
D
Jin
Peng
P
Li
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D045744:Cell Line, Tumor; D015942:Factor VIIa / Q000037:antagonists & inhibitors; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D007822:Laryngeal Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000627:therapeutic use*
D006023:Glycoproteins; D018809:Proliferating Cell Nuclear Antigen; D015842:Serine Proteinase Inhibitors; C021240:tissue-factor-pathway inhibitor 2; D015942:Factor VIIa