JNK signaling in hepatocarcinoma cells is associated with the side population upon treatment with anticancer drugs

  • Authors:
    • Jong Bin Kim
    • Seo-Young Park
    • Hye Ri Kim
    • Yeon Hwa Ahn
    • Hyeon-Gun Jee
    • Jeong‑Hoon  Lee
    • Su Jong Yu
    • Hyo-Suk Lee
    • Minjong Lee
    • Jung-Hwan Yoon
    • Yoon Jun Kim
  • View Affiliations

  • Published online on: October 23, 2014     https://doi.org/10.3892/mmr.2014.2761
  • Pages: 263-268
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Abstract

Liver cancer is one of the most drug-resistant cancer types, and cancer stem cells are related to drug resistance. c-Jun-N-terminal kinase (JNK) signaling is involved in drug resistance, and the side population of cells (SP cells) can be used as a model to study liver cancer stem cells. We sought to evaluate the relationship between SP cells and JNK signaling in hepatocarcinoma cells. For this purpose, we examined cell proliferation and the SP cell ratio following treatment of Huh7 cells with the anticancer drugs 5-fluorouracil (5-FU) and paclitaxel. The expression of phospho-stress-activated protein kinase (SAPK)/JNK in the treated cells was evaluated using immunoblotting. 5-FU and paclitaxel treatment increased the number of SP cells and JNK phosphorylation, and decreased cell survival. Huh7 and HepG2 cells were also treated with SP600125, a JNK inhibitor, to study the relationship between SP cells and JNK signaling. The increase in the number of SP cells and the SAPK/JNK and c-Jun phosphorylation was reverted by SP600125 treatment in these cells. We also used immunohistochemistry and showed that SAPK/JNK and c-Jun phosphorylation are increased in hepatocarcinoma tissues. In conclusion, our results demonstrate that the number of SP cells and SAPK/JNK phosphorylation are increased upon treatment with anticancer drugs, and that this increase is blocked by inhibition of JNK signaling. These findings suggest that drug resistance in liver cancer may involve an increase in the number of SP cells following JNK activation.
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January-2015
Volume 11 Issue 1

Print ISSN: 1791-2997
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Spandidos Publications style
Kim JB, Park S, Kim HR, Ahn YH, Jee H, Lee JH, Yu SJ, Lee H, Lee M, Yoon J, Yoon J, et al: JNK signaling in hepatocarcinoma cells is associated with the side population upon treatment with anticancer drugs. Mol Med Rep 11: 263-268, 2015.
APA
Kim, J.B., Park, S., Kim, H.R., Ahn, Y.H., Jee, H., Lee, J. ... Kim, Y.J. (2015). JNK signaling in hepatocarcinoma cells is associated with the side population upon treatment with anticancer drugs. Molecular Medicine Reports, 11, 263-268. https://doi.org/10.3892/mmr.2014.2761
MLA
Kim, J. B., Park, S., Kim, H. R., Ahn, Y. H., Jee, H., Lee, J., Yu, S. J., Lee, H., Lee, M., Yoon, J., Kim, Y. J."JNK signaling in hepatocarcinoma cells is associated with the side population upon treatment with anticancer drugs". Molecular Medicine Reports 11.1 (2015): 263-268.
Chicago
Kim, J. B., Park, S., Kim, H. R., Ahn, Y. H., Jee, H., Lee, J., Yu, S. J., Lee, H., Lee, M., Yoon, J., Kim, Y. J."JNK signaling in hepatocarcinoma cells is associated with the side population upon treatment with anticancer drugs". Molecular Medicine Reports 11, no. 1 (2015): 263-268. https://doi.org/10.3892/mmr.2014.2761