Department of Ultrasound, Dongguan People's Hospital Affiliated to Southern Medical University, No. 3 New Valley Chung Wan Road South, Wanjiang District, Dongguan, 523059, Guangdong, China.
The Third Affiliated Hospital, Center for DAMP Biology, Key Laboratory for Major Obstetrics Diseases of Guangdong Province, Key Laboratory of Protein Modification and Degradation Laboratory of Guangdong Higher Education Institutes, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, Guangdong 510510, China.
Biomed Res Int. 2019 Feb 19;2019:1937460. doi: 10.1155/2019/1937460. eCollection 2019.
To explore the antitumor effect of hypoxia-inducible factor-1 short hairpin RNA (HIF-1 shRNA) delivered by ultrasound targeted microbubble destruction (UTMD) and transcatheter arterial embolization (TAE) on rats with hepatic cancer. After the models of transplantation hepatoma were established, Wistar rats were randomly divided into 4 groups: Control group, UTMD group, TAE group, and UTMD+TAE group. Contrast-enhanced ultrasound (CEUS) was used to monitor tumor size on day 14 after four different treatments. Western blotting and immunohistochemistry were applied to measure the protein level of HIF-1 and VEGF in the hepatic cancer tissue. In comparison with UTMD+TAE group (21.25±10.68 days), the mean survival time was noticeably shorter in the Control group and TAE group (13.02±4.30 days and 15.03±7.32 days) (p<0.05, respectively). There was no statistical difference between UTMD+TAE group and UTMD group of the mean survival time (p>0.05). In addition, our results proved that the tumor sizes in UTMD+TAE group were obviously smaller than those in other groups (p<0.05, respectively). By CEUS, we clearly found that the tumor size was the smallest on day 14 in the UTMD+TAE group. The western blotting and immunohistochemistry results proved that the protein levels of HIF-1 and VEGF in UTMD+TAE group were obviously lower than those in TAE group and Control group on days 7 and 14 (p<0.05, respectively). However, there was no statistical difference between UTMD+TAE group and UTMD group (p>0.05). In this study we tried to explore the antitumor effect through a combination of UTMD-mediated HIF-1 shRNA transfection and TAE on rats with hepatic cancer. Our results showed that UTMD-mediated HIF-1 shRNA transfection and TAE can obviously silence HIF-1 and VEGF expression, thereby successfully inhibiting the growth of the tumor.
探讨超声靶向微泡破坏(UTMD)联合经导管肝动脉栓塞化疗(TAE)递送缺氧诱导因子-1 短发夹 RNA(HIF-1 shRNA)对肝癌大鼠的抗肿瘤作用。建立移植性肝癌模型后,Wistar 大鼠随机分为 4 组:对照组、UTMD 组、TAE 组和 UTMD+TAE 组。在 4 种不同治疗后第 14 天,采用超声造影(CEUS)监测肿瘤大小。Western blot 和免疫组织化学法检测肝癌组织中 HIF-1 和 VEGF 的蛋白水平。与 UTMD+TAE 组(21.25±10.68 天)相比,对照组和 TAE 组的平均生存时间明显缩短(13.02±4.30 天和 15.03±7.32 天)(p<0.05)。UTMD+TAE 组与 UTMD 组的平均生存时间无统计学差异(p>0.05)。此外,我们的结果表明,UTMD+TAE 组的肿瘤体积明显小于其他组(p<0.05)。通过 CEUS,我们清楚地发现,在 UTMD+TAE 组,肿瘤体积在第 14 天最小。Western blot 和免疫组织化学结果表明,UTMD+TAE 组在第 7 天和第 14 天 HIF-1 和 VEGF 的蛋白水平明显低于 TAE 组和对照组(p<0.05)。然而,UTMD+TAE 组与 UTMD 组之间无统计学差异(p>0.05)。在这项研究中,我们试图通过 UTMD 介导的 HIF-1 shRNA 转染联合 TAE 来探讨对肝癌大鼠的抗肿瘤作用。我们的研究结果表明,UTMD 介导的 HIF-1 shRNA 转染联合 TAE 可明显沉默 HIF-1 和 VEGF 的表达,从而成功抑制肿瘤的生长。