Epidermal growth factor receptor transactivation is involved in the induction of human hepatoma SMMC7721 cell proliferation by insufficient radiofrequency ablation

Dai,Hongliang; Jia,Guizhi; Wang,Hongxin; Yang,Jingming; Jiang,Hua; Chu,Minghui

doi:10.3892/ol.2017.6463

Epidermal growth factor receptor transactivation is involved in the induction of human hepatoma SMMC7721 cell proliferation by insufficient radiofrequency ablation

Authors:
- Hongliang Dai
- Guizhi Jia
- Hongxin Wang
- Jingming Yang
- Hua Jiang
- Minghui Chu
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Affiliations: Department of Community Health Nursing, School of Nursing, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Physiology, College of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Pharmacology, College of Basic Medical Sciences, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Pharmacognosy, College of Pharmacy, Jinzhou Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: June 22, 2017 https://doi.org/10.3892/ol.2017.6463
Pages: 2463-2467

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Abstract

Our previous study revealed that insufficient radiofrequency ablation (RFA) promotes the malignancy of human hepatocellular carcinoma (HCC) SMMC7721 cells via the Ca2+/calmodulin‑dependent protein kinase II (CaMKII)/extracellular signal‑regulated kinase (ERK)‑induced overexpression of vascular endothelial growth factor (VEGF). The aims of the present study were to address the involvement of epidermal growth factor receptor (EGFR) transactivation in the enhanced SMMC7721 cell proliferation induced by insufficient RFA, in addition to its association with the CaMKII/ERK/VEGF signaling cascade. SMMC7721 cells were subjected to a 47˚C treatment regimen to simulate insufficient RFA. Cell proliferation was determined using MTT and colony formation assays. The expression levels of VEGF, CaMKII, phosphorylated (phospho)‑CaMKII, ERK, phospho‑ERK, EGFR and phospho‑EGFR were analyzed using western blotting. The results demonstrated that the enhancement of SMMC7721 cell proliferation by the 47˚C treatment regimen was significantly inhibited by exposure of the cells to AG178 (a specific inhibitor of EGFR). Furthermore, AG1478 exposure prevented the overexpression of VEGF and phosphorylation of ERK, but had no significant effects on CaMKII phosphorylation. By contrast, 47˚C treatment‑induced EGFR phosphorylation was inhibited by treatment with KN93 (a specific inhibitor of CaMKII). Overall, the results of the present study have suggested a role for EGFR transactivation in the RFA‑promoted growth of residual HCC. Thus, targeting EGFR may represent a useful preventive and therapeutic strategy for RFA‑induced HCC progression and recurrence.

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