title: Transarterial embolization combined with RNA interference targeting hypoxia-inducible factor-1α for hepatocellular carcinoma: a preliminary study of rat model.
abstract: OBJECTIVE
  To study whether transarterial embolization (TAE) with RNA interference (RNAi) targeting hypoxia-inducible factor-1α (HIF-1α) can improve efficacy of TAE in treating hepatocellular carcinoma (HCC).
  
  
  METHODS
  CBRH-7919 rat hepatoma cell line was used and HCC models of rats were constructed. The siRNA transfection compound was made by mixing specific siRNA and Lipofectamine 2000™. Delivery and transfection of siRNA were administered by injecting iodized oil emulsion (diluted lipiodol and siRNA) via hepatic artery. The expression levels of mRNA and protein were detected using the real-time reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and western blotting assays, respectively.
  
  
  RESULTS
  In vitro experiment, the specific HIF-1α-siRNA was proved to inhibit expression levels of HIF-1α and vascular endothelial growth factor (VEGF) effectively. In animal study, real-time RT-PCR assay showed the average relative mRNA expressions of HIF-1α were 0.31 ± 0.01, 0.65 ± 0.03, 0.46 ± 0.005, and 1.00 ± 0.00 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Western blotting assay showed the average relative protein expressions of HIF-1α were 0.13 ± 0.02, 0.87 ± 0.02, 0.39 ± 0.02, and 1.02 ± 0.01 in TAE + siRNA, siRNA, TAE, and control groups, respectively. Compared with control, TAE, and siRNA groups, TAE + siRNA can significantly inhibit protein expressions of HIF-1α and VEGF (PHIF-1α< 0.001; PVEGF< 0.001). Overall survival of rats underwent TAE + siRNA was significantly longer than that of rats treated with TAE monotherapy (P = 0.001).
  
  
  CONCLUSIONS
  This animal study showed TAE combined with HIF-1α-RNAi could significantly improve efficacy of TAE in treating HCC by inhibiting expressions of HIF-1α and VEGF after TAE treatment.
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China.
authors.forename: Jia-Yan
authors.initials: JY
authors.lastname: Ni
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China. xu_lin_feng@163.com.
authors.forename: Lin-Feng
authors.initials: LF
authors.lastname: Xu
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China.
authors.forename: Qiao-Sheng
authors.initials: QS
authors.lastname: Huang
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Sun
authors.affiliation: Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Department of Interventional Radiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 West Yanjiang Road, Guangzhou, 510210, Guangdong Province, People's Republic of China.
authors.forename: Yao-Ting
authors.initials: YT
authors.lastname: Chen
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000556:secondary / Q000628:therapy*; D045744:Cell Line, Tumor; D004621:Embolization, Therapeutic; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000235:genetics*; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
keywords: Hepatocellular carcinoma; Hypoxia-inducible factor-1α; RNA interference; Transarterial embolization; Vascular endothelial growth factor