Document Type
Article
Publication Date
5-1-2012
Publication Title
Plos One
Abstract
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-1α 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-1α 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 HIF1α/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.
Recommended Citation
Kong, Jian; Kong, Jinge; Pan, Bing; Ke, Shan; Dong, Shuying; Li, Xiuli; Zhou, Aimin; Zheng, Lemin; and Sun, Wen Bing, "Insufficient Radiofrequency Ablation Promotes Angiogenesis of Residual Hepatocellular Carcinoma Via HIF-1α/VEGFA" (2012). Chemistry Faculty Publications. 396.
https://engagedscholarship.csuohio.edu/scichem_facpub/396
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
DOI
10.1371/journal.pone.0037266
Version
Publisher's PDF
Volume
7
Issue
5
