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Recombinant adenovirus mediated HSV-TK gene in vessel-targeted treatment of subcutaneously implanted HHC in mice
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Abstract:
Objective: To explore the therapeutic efficacy and mechanism of herpes simplex virus thymidine kinase (HSV-TK) in blood vessel-targeted treatment of human hepatocellular carcinoma subcutaneously implanted in mice. Methods: Thirty-two BALB/C mice were subcutaneously transplanted with human hepatocellular carcinoma and the tumors were allowed to grow till the volume reached 100 mm3, then the mice were divided into 4 groups: Ganciclovir group （Ⅰ）, Ad group （Ⅱ）, AdCMV-TK+group GCV (Ⅲ) and AdKDR-TK + GCV group (Ⅳ). Recombinant adenovirus or Ad were injected intra-tumorally in all mice. Ganciclovir (GCV) was given at a dose of 100 mg/(kg·d) (ip) on the following day of injection for 10 days. Microvessel density (MVD) of the tumors was determined with the immunohistochemical methods and the growth of the tumors was observed. Results: Compared with groupⅠ, the tumor inhibitory rate was 12.3% in group Ⅲ and 24.5% in group Ⅳ; the inhibition rates were significantly different between group Ⅲ and IV (P<0.05). The mean MVD in group Ⅰ, Ⅱ, Ⅲ and Ⅳ was 37.4±8.6，30.6±7.8，27.6±7.1，and 10.7±4.1(microvessels/mm2) , respectively; significant differences were found between group Ⅲ and Ⅱ(P<0.05)，Ⅳ and Ⅱ(P<0.01)，and Ⅳ and Ⅲ (P<0.01). Conclusion: Our results suggest that AdKDR-TK may effectively restrain the growth of hepatocellular carcinoma through inhibiting angiogenesis.
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