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

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.

Modelling of combination therapy using implantable anticancer drug delivery with thermal ablation in solid tumor

“…Thus, thermal ablation will destroy the cellular and vasculature structures, which results in a new ablated tissue with different characteristics. However, the main limitation and challenge of thermal ablation is the risk of local recurrence and residual tumor after the thermal ablation, particularly at the tumor periphery 3 – 5 . The experimental studies showed that the combination therapy through local release of anticancer drugs from a miniaturized implant in solid tumors following thermal ablation can result in a better therapeutic efficacy by destroying the residual cancer cells and preventing tumor recurrence 6 – 8 .…”

Impact of Elevated Circulating Histones on Systemic Inflammation after Radiofrequency Ablation in Lung Cancer Patients

“…As a minimally invasive approach, RFA has been widely used as the favorable therapeutic strategies for lung cancer patients when surgical resections are not feasible. The major problem with RFA is that an exaggerated systemic inflammatory response may occur during treatment [ 5 , 6 ]. It has been reported that RFA can induce cytokine production, which may alter the local and systemic immune environment [ 7 ].…”

The influence of liposomal quercetin on liver damage induced by microwave ablation

“…Wan et al . found that incomplete RFA treatment promoted HSP70 and HIF-1α expression in the transition area 17 . HSP70 interfered with the signaling pathways and cellular responses to hypoxic stress and influenced the stability of HIF-1α 18 .…”