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.%目的 血管毁损术治疗肿瘤后,肿瘤血管均有不同程度的再生,导致肿瘤坏死不彻底,其核心可能与HIF-1α的高表达有关.本研究探讨采用载HIF-1α反义寡核苷酸微泡联合超声抑制肿瘤生长的可行性.材料与方法 24只荷皮下VX2肿瘤的新西兰大白兔随机分为新型微泡超声组(n=8)、普通微泡超声组(n=8)和单纯超声组(n=8).新型微泡超声组经耳缘静脉推注载HIF-1α反义寡核苷酸微泡联合超声辐照,普通微泡超声组和单纯超声组分别以普通微泡、生理盐水代替.每次10 min,每72 h治疗一次,采集各时间点肿瘤二维超声图像,测量肿瘤切面最大直径.结果 在30 d的实验周期内,新型微泡超声组、普通微泡超声组和单纯超声组的肿瘤平均直径由(1.13±0.19) cm、(1.17±0.21) cm、(1.22±0.17) cm生长至(1.60±0.45) cm、(2.11±0.57) cm、(3.43±0.71) cm.治疗前,3组肿瘤平均直径差异无统计学意义(P＞0.05);治疗后,新型微泡超声组肿瘤生长最缓慢,直径显著小于普通微泡超声组和单纯超声组,差异有统计学意义(P＜0.05).结论 采用载HIF-1α反义寡核苷酸微泡联合超声治疗可以明显增强普通微泡超声的血管毁损作用,有望成为一种新的肿瘤治疗方法.
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