Ultrasound-guided RNA interference targeting HIF-1 alpha improves the effects of transarterial chemoembolization in rat liver tumors

Abstract

Cheng-Shi Chen,1,2,* Qing Zhao,1,* Sheng Qian,1 Hai-Liang Li,2 Chen-Yang Guo,2 Wei Zhang,1 Zhi-Ping Yan,1 Rong Liu,1 Jian-Hua Wang1 1Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, Henan Cancer Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China *These authors contributed equally to this work Aim: To investigate whether ultrasound-guided RNA interference (RNAi) targeting hypoxia-inducible factor-1alpha (HIF-1α) can enhance the efficacy of transarterial chemoembolization (TACE) in treating hepatocellular carcinoma.Materials and methods: Rats with orthotopic hepatocellular carcinoma were randomized to four groups and treated as follows: 1) control; 2) siHIF-1α; 3) TACE; 4) siHIF-1α+TACE. Lentivirus (4×108 transfection units) with or without small interfering RNA (siRNA) expression in 0.6 mL transduction reagent was injected into tumors using a standard 1 mL syringe under ultrasonic guidance. In the siHIF-1α+TACE and siHIF-1α groups, rats received siRNA-expressing lentivirus; the rats in the TACE and control groups received lentivirus without siRNA. TACE was performed by placing a microcatheter into the gastroduodenal artery.Results: The median survival time, body weight, and tumor volume of the siHIF-1α+TACE group were better than those of the TACE, siHIF-1α, and control groups. A comparative analysis of the different treatment groups demonstrated that HIF-1α RNAi could downregulate the levels of HIF-1α and VEGF, inhibit tumor angiogenesis, and lessen metastases; all of these effects were enhanced by TACE.Conclusion: HIF-1α RNAi, which was administered in vivo in liver tumors under ultrasound guidance, improved the efficacy of TACE in treating hepatocellular carcinoma in an animal model. Keywords: transarterial chemoembolization, hypoxia-inducible factor-1alpha, hepatocellular carcinoma, ultrasound guidance, RNA interference