Chen ChengShi, Wang JianHua, Liu Rong, Qian Sheng
Department of Radiology, Zhong Shan Hospital, Fudan University, No.180 Fenglin Road, Shanghai 200032, China.
Tumour Biol. 2012 Aug;33(4):1095-103. doi: 10.1007/s13277-012-0349-8. Epub 2012 Mar 10.
Transcatheter arterial embolization (TAE) and transcatheter arterial chemoembolization are widely used palliative treatments for patients with nonsurgical hepatocellular carcinoma. TAE has been shown to increase levels of hypoxia-inducible factor-1 alpha (HIF-1α) in tumors. In this study, we investigated whether RNA interference (RNAi) of HIF-1α could improve the efficacy of TAE to treat HCC. Four treatment groups were assessed using a rat allograft model of HCC: RNAi of HIF-1α combined with TAE, RNAi of HIF-1α only, TAE only, and a control group. Rats were treated by TAE by retrograde placement of a microcatheter into the gastroduodenal artery. The results demonstrated that the RNAi of HIF-1α visibly reduced the expression of HIF-1α and vascular endothelial growth factor, suppressed tumor angiogenesis, and attenuated metastasis, which were all enhanced by TAE. The RNAi of HIF-1α synergized with TAE to significantly inhibit tumor growth. In conclusion, RNAi of HIF-1α augmented the therapeutic effects of TAE and diminished its undesirable effects.
经导管动脉栓塞术(TAE)和经导管动脉化疗栓塞术是广泛应用于无法手术的肝细胞癌患者的姑息性治疗方法。TAE已被证明会增加肿瘤中缺氧诱导因子-1α(HIF-1α)的水平。在本研究中,我们调查了HIF-1α的RNA干扰(RNAi)是否能提高TAE治疗肝癌的疗效。使用肝癌大鼠同种异体移植模型评估了四个治疗组:HIF-1α的RNAi联合TAE、仅HIF-1α的RNAi、仅TAE以及一个对照组。通过将微导管逆行置入胃十二指肠动脉对大鼠进行TAE治疗。结果表明,HIF-1α的RNAi明显降低了HIF-1α和血管内皮生长因子的表达,抑制了肿瘤血管生成,并减弱了转移,而TAE则增强了这些作用。HIF-1α的RNAi与TAE协同作用,显著抑制肿瘤生长。总之,HIF-1α的RNAi增强了TAE的治疗效果,并减少了其不良影响。