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
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.
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 (4×10(8) 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.