ABSTRACT
Purpose After the angiotripsy treatment of tumor,tumor blood vessels have different degrees of regeneration,leading to incomplete tumor necrosis,which may be related to the high expression of HIF-lα.To explore the feasibility of microbubble with HIF-1α antisense oligonucleotide combined with ultrasound inhabit tumor growth.Materials and Methods Twenty-four rabbits with VX2 tumor were randomly assigned to three groups:microbubbles with HIF-1α antisense oligonucleotide plus ultrasound (HMB+US) (n=8),microbubbles plus ultrasound (MB+US) (n=8),therapeutic ultrasound alone without microbubbles (US) (n=8).Pulsed focused ultrasound was delivered directly to the tumor surface for 10 minutes during intravenous infusion of microbubbles with HIF-1α antisense oligonucleotide in the experimental group.The control groups were applied only microbubbles or saline injection.The procedure was repeated every 72 hours until the 30th day.Contrast enhanced US and grey scale ultrasonography were acquired after every treatment to get the tumor perfusion images,size and volume measurements.Results The average maximum diameter of the HMB+US,MB+US,and the US groups grows from (1.13±0.19) cm,(1.17±0.21) cm,(1.22±0.17) cm to (1.60±0.45) cm,(2.11 ±0.57) cm,(3.43 ± 0.71) cm within a 30d-experimental period,respectively.No statistical difference in average diameter was observed among three groups before treatment (P＞0.05).The average maximum diameter of the HMB+US group was significantly smaller than that of the two control groups at the end of experiment (P＜0.05),and the average maximum diameter of the MB+US group was significantly smaller than that of the US group (P＜0.05).Conclusion Microbubbles with HIF-1α antisense oligonucleotide can enhance vascular damage effect ofangiotripsy,which can be a novel method for tumor treatment.