|Insufficient Radiofrequency Ablation Promotes Angiogenesis of Residual Hepatocellular Carcinoma via HIF-1 alpha/VEGFA|
|Kong, Jian1; Kong, Jinge2,3,4; Pan, Bing2,3,4; Ke, Shan1; Dong, Shuying1; Li, Xiuli5; Zhou, Aimin6; Zheng, Lemin2,3,4; Sun, Wen-bing1|
|WOS标题词||Science & Technology|
|研究领域[WOS]||Science & Technology - Other Topics|
|关键词[WOS]||ENDOTHELIAL GROWTH-FACTOR ; COLORECTAL LIVER METASTASES ; INDUCIBLE FACTOR 1-ALPHA ; SQUAMOUS-CELL CARCINOMA ; TUMOR ANGIOGENESIS ; RAPID PROGRESSION ; THERMAL ABLATION ; VEGF EXPRESSION ; KEY MEDIATOR ; HYPOXIA|
Background: The mechanism of rapid growth of the residual tumor after radiofrequency (RF) ablation is poorly understood. In this study, we investigated the effect of hyperthermia on HepG2 cells and generated a subline with enhanced viability and dys-regulated angiogenesis in vivo, which was used as a model to further determine the molecular mechanism of the rapid growth of residual HCC after RF ablation.
Methodology/Principal Findings: Heat treatment was used to establish sublines of HepG2 cells. A subline (HepG2 k) with a relatively higher viability and significant heat tolerance was selected. The cellular protein levels of VEGFA, HIF-1 alpha and p-Akt, VEGFA mRNA and secreted VEGFA were measured, and all of these were up-regulated in this subline compared to parental HepG2 cells. HIF-1 alpha inhibitor YC-1 and VEGFA siRNA inhibited the high viability of the subline. The conditioned media from the subline exerted stronger pro-angiogenic effects. Bevacizumab, VEGFA siRNA and YC-1 inhibited proangiogenic effects of the conditioned media of HepG2 k cells and abolished the difference between parental HepG2 cells and HepG2 k cells. For in vivo studies, a nude mouse model was used, and the efficacy of bavacizumab was determined. HepG2 k tumor had stronger pro-angiogenic effects than parental HepG2 tumor. Bevacizumab could inhibit the tumor growth and angiogenesis, and also eliminate the difference in tumor growth and angiogenesis between parental HepG2 tumor and HepG2 k tumor in vivo.
Conclusions/Significance: The angiogenesis induced by HIF1 alpha/VEGFA produced by altered cells after hyperthermia treatment may play an important role in the rapid growth of residual HCC after RF ablation. Bevacizumab may be a good candidate drug for preventing and treating the process.
|项目编号||30872490 ; 30900595 ; 81172500 ; 81170101 ; 2010CB912504 ; 2011CB503900 ; 7102104 ; 2009J01112|
|资助机构||National Natural Science Foundation of China ; "973" National S& ; T Major Project ; Natural Science Foundation of Beijing ; Natural Science Foundation of Fujian|
|作者单位||1.Capital Med Univ, Beijing Chao Yang Hosp, Dept Hepatobiliary Surg, Beijing, Peoples R China|
2.Peking Univ, Hlth Sci Ctr, Minist Educ, Inst Cardiovasc Sci, Beijing 100871, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Minist Educ, Inst Syst Biomed,Sch Basic Med Sci, Beijing 100871, Peoples R China
4.Peking Univ, Hlth Sci Ctr, Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100871, Peoples R China
5.Chinese Peoples Liberat Army Gen Hosp, Dept Gynecol & Obstet, Beijing, Peoples R China
6.Cleveland State Univ, Dept Chem, Clin Chem Program, Cleveland, OH 44115 USA
|Kong, Jian,Kong, Jinge,Pan, Bing,et al. Insufficient Radiofrequency Ablation Promotes Angiogenesis of Residual Hepatocellular Carcinoma via HIF-1 alpha/VEGFA[J]. PLOS ONE,2012,7(5).|
|APA||Kong, Jian.,Kong, Jinge.,Pan, Bing.,Ke, Shan.,Dong, Shuying.,...&Sun, Wen-bing.(2012).Insufficient Radiofrequency Ablation Promotes Angiogenesis of Residual Hepatocellular Carcinoma via HIF-1 alpha/VEGFA.PLOS ONE,7(5).|
|MLA||Kong, Jian,et al."Insufficient Radiofrequency Ablation Promotes Angiogenesis of Residual Hepatocellular Carcinoma via HIF-1 alpha/VEGFA".PLOS ONE 7.5(2012).|
|journal.pone.0037266（2259KB）||期刊论文||作者接受稿||开放获取||CC BY-NC-SA||浏览 请求全文|