Incomplete radiofrequency ablation accelerates proliferation and angiogenesis of residual lung carcinomas via HSP70/HIF-1α

Wan,Jun; Wu,Wei; Huang,Yunlong; Ge,Wei; Liu,Shandong

doi:10.3892/or.2016.4858

Incomplete radiofrequency ablation accelerates proliferation and angiogenesis of residual lung carcinomas via HSP70/HIF-1α

Authors:
- Jun Wan
- Wei Wu
- Yunlong Huang
- Wei Ge
- Shandong Liu
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Affiliations: Department of Thoracic Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of Hematology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China
Published online on: June 7, 2016 https://doi.org/10.3892/or.2016.4858
Pages: 659-668
Copyright: © Wan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Radiofrequency ablation (RFA) therapy has been proved effective and feasible for lung cancer. However, the molecular mechanisms of local lung cancer recurrence following RFA are poorly understood. The present study aimed to evaluate the ability of HSP70/HIF-1α to affect the proliferation and angiogenesis of non-small cell lung cancers (NSCLCs) following insufficient RFA to uncover the molecular mechanisms of local recurrence. In vitro heat treatment was used to establish sublines of NCI-H1650 cells. The NCI-H1650 subline that was established by heat treatment at 54˚C had a relatively higher viability and significantly elevated heat tolerance (compared to the parental strain). After treatment with the HSP70 inhibitor VER-155008, the HIF-1α inhibitor YC-1 and PI3K/Akt inhibitor wortmannin, the viability and proliferation rate of the cells was measured. At the same time, HSP70, HIF-1α and Akt were detected by real-time PCR and western blotting. In vivo xenograft tumors were created by subcutaneously inoculating nude mice with NCI-H1650 cells. HSP70, HIF-1α and Akt were detected by western blotting, and CD34 expression was detected by immunohistochemistry before and after RFA or treatment with the VER-155008, YC-1 or wortmannin inhibitors. The heat-adapted NCI-H1650 subline established in vitro had a higher viability and proliferative activity compared to parental cells. Inhibiting HSP70/HIF-1α abolished this difference. Blocking the PI3K/Akt signaling pathway decreased HSP70/HIF-1α expression levels. In vivo, we found that incomplete RFA treatment promoted HSP70/HIF-1α and CD34 expression. Additionally, the combination of RFA and treatment targeting HSP70/HIF-1α resulted in a synergistic reduction in tumor growth compared to incomplete RFA alone. The PI3K/Akt signaling pathway is also involved in regulating HSP70/HIF-1α expression during this process. We conclude that the accelerated proliferation and angiogenesis potential of residual lung carcinomas following RFA treatment was induced by HSP70/HIF-1α, expression of which is regulated by the PI3K/Akt signaling pathway.

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