The Combined Treatment Of Liver Cancer With HIF-1αshRNA Delivered By Ultrasound-targeted Microbubbles Destruction And TAF

Background The activation and overexpression of hypoxia-inducible factor-1alpha (HIF-la) are critical factors of recurrence and metastasis of hepatic carcinoma after transcatheter arterial embolization (TAE).Objective In order to inhibit the overexpression from TAE, ultrasound targeted microbubbles destruction was used to transfer HIF-la shRNA into carcinoma cells. Methods1. Design and construct the small hairpin RNA (shRNA) expression vector targeting HIF-la;2. Mixed with shRNA expression plasmids and SonoVue, cultured rat heptatic cancer cell lines walker256with hypoxia were oscillated with ultrasound. Then the effect on gene silencing of HIF-1α was studied;3. Orthotopic transplantation tumor models of hepatic carcinoma were established on wistar rats. The mixture of HIF-1α shRNA plasmids and microbubbles were injected through tail vein and the tumors were sonicated with ultrasound simultaneously. TAE treatments were carried out after sonication. The rodents were allocated into4groups:control group (no treatment), UMTD group (treated with UTMD), TAE group, and TAE+UTMD group.Results1. The shRNA expression plasmids targeting HIF-1α were successfully constructed.2. Ex-vivo studies showed that HIF-1α shRNA significantly inhibited the expression of HIF-la in the waker256cells with hypoxia.3. In vivo studies displayed that the tumors without treatment enlarged continuously, those treated with TAE showed relapse, whereas UTMD slowed the tumor grouth, and the combined treatment of TAE and UTMD significantly suppressed the tumors.Conclusions UTMD can successfully deliver HIF-1α shRNA into the liver cancer cells, silence the expression of HIF-1α, and improve the therapatic effect of TAE.