Meloxicam combined with sorafenib synergistically inhibits tumor growth of human hepatocellular carcinoma cells via ER stress-related apoptosis

  • Authors:
    • Jingtao Zhong
    • Peng Xiu
    • Xiaofeng Dong
    • Fuhai Wang
    • Honglong Wei
    • Xin Wang
    • Zongzhen Xu
    • Feng Liu
    • Tao Li
    • Yong Wang
    • Jie Li
  • View Affiliations

  • Published online on: August 6, 2015     https://doi.org/10.3892/or.2015.4181
  • Pages: 2142-2150
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Abstract

Sorafenib (SOR) is a promising treatment for advanced hepatocellular carcinoma (HCC). However, the precise mechanisms of toxicity and drug resistance have not been fully explored and new strategies are urgently needed for HCC therapy. Meloxicam (MEL) is a selective cyclooxygenase-2 (COX-2) inhibitor which elicits antitumor effects in human HCC cells. In the present study, we investigated the interaction between MEL and SOR in human SMMC‑7721 cells and the role endoplasmic reticulum (ER) stress exerts in the combination of SOR with MEL treatment-induced cytotoxicity. Our results revealed that the combination treatment synergistically inhibited cell proliferation and enhanced apoptosis. Furthermore, the combination treatment enhanced ER stress-related molecules which involved in SMMC-7721 cell apoptosis. GRP78 knockdown by siRNA or co-treatment with MG132 significantly increased this combination treatment-induced apoptosis. In addition, we found that the combination treatment suppressed tumor growth by way of activation of ER stress in in vivo models. We concluded that the combination of SOR with MEL treatment-induced ER stress, and eventually apoptosis in human SMMC-7721 cells. Knockdown of GRP78 using siRNA or proteosome inhibitor enhanced the cytotoxicity of the combination of SOR with MEL-treatment in SMMC-7721 cells. These findings provided a new potential treatment strategy against HCC.
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October-2015
Volume 34 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhong J, Xiu P, Dong X, Wang F, Wei H, Wang X, Xu Z, Liu F, Li T, Wang Y, Wang Y, et al: Meloxicam combined with sorafenib synergistically inhibits tumor growth of human hepatocellular carcinoma cells via ER stress-related apoptosis. Oncol Rep 34: 2142-2150, 2015
APA
Zhong, J., Xiu, P., Dong, X., Wang, F., Wei, H., Wang, X. ... Li, J. (2015). Meloxicam combined with sorafenib synergistically inhibits tumor growth of human hepatocellular carcinoma cells via ER stress-related apoptosis. Oncology Reports, 34, 2142-2150. https://doi.org/10.3892/or.2015.4181
MLA
Zhong, J., Xiu, P., Dong, X., Wang, F., Wei, H., Wang, X., Xu, Z., Liu, F., Li, T., Wang, Y., Li, J."Meloxicam combined with sorafenib synergistically inhibits tumor growth of human hepatocellular carcinoma cells via ER stress-related apoptosis". Oncology Reports 34.4 (2015): 2142-2150.
Chicago
Zhong, J., Xiu, P., Dong, X., Wang, F., Wei, H., Wang, X., Xu, Z., Liu, F., Li, T., Wang, Y., Li, J."Meloxicam combined with sorafenib synergistically inhibits tumor growth of human hepatocellular carcinoma cells via ER stress-related apoptosis". Oncology Reports 34, no. 4 (2015): 2142-2150. https://doi.org/10.3892/or.2015.4181