The effect of HIFU combined with nanoscale ultrasound molecular probes with simple virus thymidine kinase gene on angiogenesis in the nude mouse tumor / 重庆医学

ABSTRACT

Objective To observe the change of the protein and gene expression of hypoxia inducing factor-1α(HIF-1a) and vascular endothelial growth factor (VEGF) in the nude mouse tumor,which has been treated by HIFU combined with nanoscale ultrasound molecular probes with HSV1-TK gene microvascular density.Methods Sixty nude mice were implanted with HepG2 Cells to establish subcutaneous transplanted tumor.Divided this mice into six groups at random after treated by HIFUMB+ HSV-TK+ GPC3 (group A),MB + HSV-TK (group B),HSV-TK +GPC3 (group C),HSV-TK (group D),MB + GPC3 (group E),PBS (group F).They were injected into the tail vein every after 3 days.Mice in group A,B,D and E were exposed to ultrasound by 2 W/cm2,1 MHz,5 mintues and 0.2 mL ganciclovi(GCV) was intraperitoneally injected at the first 48 hours after injection.After the treatment,immunohistoche were used to detect the microvascular density(MVD),Western blot and immunohistoche was employed to test the protein change of the VEGF and HIF-1α,Q-PCR was used to test the mRNA gene transcription of VEGF and HIF-1α in the tumor tissues.Results After 14 days,the protein expression of HIF-1α and VEGF in group A was significantly lower than that in group B,C,D,E and F (P＜0.05),the MVD level in the tumor is also like this,and the difference is statistically significant.Conclusion Anoscale ultrasound molecular probes with HSV1-TK can reduce the the level of VEGF,MVD and HIF-1α in the tumor which has been treated by HIFU,so it can inhibit tumor growth and improve the therapeutic efficacy after HIFU treatment.