The Effect Of Hifu Combined With Nanoscale Ultrasound Molecular Probes With Simple Virus Thymidine Kinase Gene(hsv1-tk) On Angiogenesis In The Nude Mouse Tumor

BackgroundHepatocellular carcinoma is a common malignant tumor in thedigestive, because it is concealment, easy to local invasion and distantmetastasis, the majority of patients in clinic has lost the opportunity tosurgical excision, so local adjuvant therapy has become more and moreimportant in clinical. As a kind of local heat treatment and non-invasivetechnology, high intensity focused ultrasound(HIFU) has become one ofthe important means of treatment for liver cancer[1]. But due to the shade ofrib bow shade, the position, and the influence of various factors such asultrasonic energy attenuation, HIFU treatment is difficult to kill tumor cellscompletely, thus there will be residual tumor and recurrence[2]. Therefor, itis important to search new treatment measures and improve the therapeuticeffect of HIFU.ObjectiveTo observe the change of microvascular density (MVD), the gene and protein expression of vascular endothelial growth factor (VEGF) andhypoxia inducing factor-1α(HIF-1α) in the nude mouse tumor, which hasbeen treated by HIFU combined with nanoscale ultrasound molecularprobes with HSV1-TK gene, the mechanism is also explored.MethodsA total of60nude mice were implanted to establish subcutaneoustransplanted tumor. After treated by HIFU, divided this mice into sixgroups at random: ultrasonic irradiate nanoscale ultrasound molecularprobes with gene group(group A), ultrasonic irradiate microbubble withgene group(groupB), nanoscale ultrasound molecular probes with genegroup(group C), ultrasonic irradiate gene group(group D), ultrasonicirradiate nanoscale ultrasound molecular probes group(group E) and controlgroup(group F). After the treatment, Western blot and immunohistoche areused to detect the protein change of HIF-1α and VEGF, the mRNA genetranscription of HIF-1α and VEGF are detected by Q-PCR.immunohistochemestry is employed to test the MVD in the tumor tissues.Results14days after treatment, the immunohistochemestry, Q-PCR andwestern blot show that the level of the MVD, transcription and proteinexpression of HIF-1α and VEGF in group C, D, E and F weresignificantly higher than that of group B (P<0.05), but the indicators ingroup B was higher than group A (P<0.05), the difference is statistically significant.ConclusionHIFU combined with anoscale ultrasound molecular probes withsimple virus thymidine kinase gene (HSV1-TK) treatment can reduce theHIF-1α, VEGF and its gene exprssion in the residual tumor after HIFUtreatment, this method can inhibit the formation of tumor angiogenesis andtumor growth, and improve the therapeutic efficacy after HIFU treatment.