c-Met/MAPK pathway promotes the malignant progression of residual hepatocellular carcinoma cells after insufficient radi

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ORIGINAL PAPER

c‑Met/MAPK pathway promotes the malignant progression of residual hepatocellular carcinoma cells after insufficient radiofrequency ablation Guoqun Jia1 · Fengjuan Li3 · Ruiying Tong2 · Ying Liu2 · Mengna Zuo2 · Libing Ma2   · Xiang Ji2 Received: 15 October 2020 / Accepted: 14 November 2020 / Published online: 19 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract Radiofrequency ablation (RFA) is popularly used in the treatment of hepatocellular carcinoma (HCC). However, the accelerated malignant progression of residual HCC cells after RFA is the main obstacle for the application of this technology in HCC treatment. In the present study, HepG2 cells, an established human HCC cell line, experienced repeatedly with heat treatment, survived cells, HepG2-H cells, were used to simulate residual HCC cells after RFA. The abilities of proliferation, colony formation, and migration were compared between HepG2 and HepG2-H cells. Then, RNA sequencing was used to explore the difference in genes expression between two groups of cells. Subsequently, the level of c-Met, one of membranous receptors of MAPK signal pathway, was measured by RT-qPCR and western blot; the effect of c-Met inhibition on the malignant progression of HepG2-H cells was evaluated. The results showed that HepG2-H cells exhibited higher abilities in the proliferation, colony formation, and migration than that of HepG2 cells. Moreover, differentially expressed genes between two groups of cells were prominently enriched in MAPK signal pathway. The level of c-Met in HepG2-H cells was significantly higher than that in HepG2 cells, and the inhibition in the activity of c-Met could repress the malignant behaviors of HepG2-H cells. These results indicated that the accelerated malignant progression of residual HCC cells after RFA can be partly attributed to the overexpression of c-Met and the activation of MAPK signal pathway. Therefore, we proposed that RFA followed by c-Met inhibitor intake maybe is a better treatment protocol for HCC. Keywords  Radiofrequency ablation · c-Met · MAPK signal pathway · Hepatocellular carcinoma

Introduction

Guoqun Jia and Fengjuan Li are co-first authors. * Libing Ma mlb‑[email protected] * Xiang Ji [email protected] 1



Department of General Surgery, The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science & Technology, Baotou, Inner Mongolia, China

2



School of Life Science and Technology, Inner Mongolia University of Science & Technology, Baotou, Inner Mongolia, China

3

Department of Neurology, Baotou Eighth Hospital, Baotou, Inner Mongolia, China



Hepatocellular carcinoma (HCC) is the most common type of primary liver tumor, ranks the fifth most common tumor in the world, and the third malignant tumor in terms of mortality [1]. Radiofrequency ablation (RFA) is  widely used  as an effective treatment of liver tumors, and is considered to be the first line of treatment for unresectable early HCC, with a rate of complete necrosis well

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