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

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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.

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Data availability

The raw data used to support the findings of this study are available from the corresponding authors upon request.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China [Grant Nos. 41666007 and 31660340]; Natural Science Foundation of Inner Mongolia Autonomous Region of China [Grant Nos. 2018MS03062 and 2019MS02024].

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Author notes

  1. Guoqun Jia and Fengjuan Li are co-first authors.

Authors and Affiliations

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

    Guoqun Jia

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

    Ruiying Tong, Ying Liu, Mengna Zuo, Libing Ma & Xiang Ji

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

    Fengjuan Li

Authors
  1. Guoqun Jia
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  2. Fengjuan Li
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  4. Ying Liu
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  5. Mengna Zuo
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Contributions

LM and XJ (co-corresponding authors) designed the research and wrote the paper; GJ and FL (co-first authors) performed the most of experiments, RT, MZ and YL participated in some of experiments. All authors read and approved the final manuscript.

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Correspondence to Libing Ma or Xiang Ji.

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Jia, G., Li, F., Tong, R. et al. c-Met/MAPK pathway promotes the malignant progression of residual hepatocellular carcinoma cells after insufficient radiofrequency ablation. Med Oncol 37, 117 (2020). https://doi.org/10.1007/s12032-020-01444-z

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  • DOI: https://doi.org/10.1007/s12032-020-01444-z

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