Treatment for Liver Tumor Using Combined Transarterial Embolization and Interaarterial Transfecting HIF-1α shRNA in a Rabbit VX2 Model

Chuangen Guo,1 Cheng Wang,2 Jingfeng Zhang,1,3 Xiao Chen4 1Department of Radiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310003, People’s Republic of China; 2Department of Radiology, Nanjing Drum Tower Hospital, Nanjing University, Nanjing, Jiangsu Province 210029, People’s Republic of China; 3Department of Radiology, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang Province 315010, People’s Republic of China; 4Department of Radiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province 210029, People’s Republic of ChinaCorrespondence: Jingfeng Zhang Email zyyfy001@sina.cnBackground: Hypoxia-inducible factor-1α (HIF-1α) has been selected as therapeutic gene in gene therapy. The aim of this study was to explore the treatment effect of combined transarterial embolization using microsphere treatment (MD) and intraarterial transfecting HIF-1α shRNA on hepatocellular carcinoma (HCC).Materials and Methods: Rabbit skin fibroblast was transfected with HIF-1α shRNA to evaluate the knocking down efficiency. Sixteen rabbit VX2 liver tumor models were randomly divided into four groups: the control group without any treatment, the MD group, the shRNA group (HIF-1α shRNA transfection by transcatheter intraarterial infusion), and the shRNA+MD group. The necrotic score, mitotic count and expression of HIF-1α, vascular endothelial growth factor (VEGF), CD34 and periodic acid-Schiff (PAS) stain were evaluated at the 14th and 28th day after treatment. The expression of HIF-1α and VEGF of VX2 tumors was also evaluated by real-time polymerase chain reaction on the 28th day.Results: The expression of HIF-1α-mRNA was lower in HIF-1α shRNA group than the control (p < 0.01). The tumor size was smaller in the shRNA + MD group than the shRNA group and the MD group (p < 0.05) on the 28th day. The growth rate of tumors in the shRNA + MD group was also lower than in other groups. The gene and protein expressions of both HIF-1α and VEGF in the shRNA + MD group were lower than the MD group, shRNA group and control group on the 28th day (p < 0.05). The necrotic score was higher in the shRNA + MD group than the MD group and control group (p < 0.05). The mitotic count and PAS-positive cells in shRNA + MD group were lower and CD34 was higher than the other three groups (p < 0.05).Conclusion: Compared to therapy with MD or HIF-1α shRNA with transcatheter intraarterial transfection alone, the combined treatment has a better effect on HCC.Keywords: hepatocellular carcinoma, transarterial embolization, hypoxia-inducible factor-1α, shRNA