title: Sorafenib suppresses the rapid progress of hepatocellular carcinoma after insufficient radiofrequency ablation therapy: an experiment in vivo.
abstract: BACKGROUND
  Radiofrequency ablation (RFA) is a widely applied treatment for hepatocellular carcinoma (HCC), but insufficient RFA can promote rapid progression of the residual tumor through the hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) pathway. Although sorafenib has been successfully applied to advanced HCC, the use of sorafenib in residual tumor cells after RFA has rarely been tested.
  
  
  OBJECTIVE
  To evaluate the potential role of sorafenib as an adjunct to RFA to reduce the recurrence rate after insufficient RFA.
  
  
  METHODS
  Xenograft tumors of SMMC 7721 were created by subcutaneously inoculating nude mice with hepatoma cells (5 × 10(6) cells per mouse). Fourteen days after inoculation, all mice were divided into three groups (control group [sham puncture], RFA group, and RFA combined with sorafenib treatment group) with six mice in each group. Each group was given a different treatment procedure. After treatment, the volume of the tumors was calculated from the resected specimens. The mRNA and protein expression of HIF-1α and VEGFA was quantified by real-time PCR and immunohistochemistry analysis. The micro-vessel density (MVD) was determined by CD34 immunohistochemistry.
  
  
  RESULTS
  Real-time PCR and immunohistochemistry analysis showed that, compared to the RFA group, HIF-1α and VEGFA expression were significantly decreased in the group that received RFA combined with sorafenib treatment (P < 0.05). By comparing the control group with the RFA group, we found that insufﬁcient RFA promoted HIF-1α and VEGFA expression (P < 0.05). Similar results were obtained for MVD expression. Additionally, the combination of RFA with sorafenib therapy resulted in a synergistic reduction in tumor growth compared to insufficient RFA and sham puncture (P < 0.05).
  
  
  CONCLUSIONS
  Sorafenib was able to inhibit the expression of HIF-1α and VEGFA, and sorafenib was able to increase time to recurrence when used as an adjunct to RFA.
authors.affiliation: Department of Medical Ultrasonics, the First Affiliated Hospital, Institute of Diagnostic and Interventional Ultrasound, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.forename: Xiao-hua
authors.initials: XH
authors.lastname: Xie
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Xie
authors.forename: Zuo-feng
authors.initials: ZF
authors.lastname: Xu
authors.forename: Guang-jian
authors.initials: GJ
authors.lastname: Liu
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Zheng
authors.forename: Guang-liang
authors.initials: GL
authors.lastname: Huang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Shu-guang
authors.initials: SG
authors.lastname: Zheng
authors.forename: Ming-de
authors.initials: MD
authors.lastname: Lü
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017115:Catheter Ablation; D003131:Combined Modality Therapy; D018450:Disease Progression; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007150:Immunohistochemistry; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D060888:Real-Time Polymerase Chain Reaction; D000077157:Sorafenib; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010671:Phenylurea Compounds; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000077157:Sorafenib