Growth suppression of human laryngeal squamous cell carcinoma by adenovirus-mediated tissue factor pathway inhibitor gene 2.

ABSTRACT

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). STUDY DESIGN: 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. CONCLUSION: 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.