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Article

Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line

  • Authors:
    • Rong Gui
    • Dengqing Li
    • Guannan Qi
    • Ali Suhad
    • Xinmin Nie
  • View Affiliations / Copyright

    Affiliations: Clinical Laboratory Centre of the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Clinical Laboratory Centre of the Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China, Hormones and Cancer Research Unit, Royal Victoria Hospital, McGill University, Quebec H3A 1A1, Canada
  • Pages: 566-570
    |
    Published online on: June 27, 2012
       https://doi.org/10.3892/ol.2012.774
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Abstract

The nitroreductase oxidored‑nitro domain containing protein 1 (NOR1) gene may be involved in the chemical carcinogenesis of hepatic cancer and nasopharyngeal carcinoma (NPC). We have previously demonstrated that NOR1 overexpression is capable of converting the monofunctional alkylating agent 5‑(aziridin‑1‑yl)‑2,4‑dinitrobenzamide (CB1954) into a toxic form by reducing the 4‑nitro group of CB1954. Toxic CB1954 is able to enhance cell killing in the NPC cell line CNE1; however, the underlying mechanisms remain unknown. Using cDNA microarrays and quantitative real‑time PCR, we previously discovered that NOR1 increases the expression of growth factor receptor‑bound protein 2 (Grb2) mRNA by 4.8‑fold in the human hepatocellular carcinoma cell line HepG2. In the present study, we revealed that NOR1 increased Grb2 protein expression by 3‑fold in HepG2 cells. Additionally, we demonstrated that NOR1 enhanced CB1954‑induced cell killing in HepG2 cells, and cell cytotoxicity was inhibited with the tyrosine kinase inhibitor genistein, or by stable transfection of Grb2 small hairpin RNA (shRNA) pU6+27‑shGrb2 to silence the expression of Grb2. Western blot analysis revealed that Grb2 downregulation may reduce the activity of the mitogen‑activated protein kinase (MAPK). Inhibiting the activation of MAPK using the methyl ethyl ketone (MEK) inhibtor PD98059 suppressed CB1954‑induced cell killing. These results suggested that the NOR1 gene enhances CB1954‑mediated cell cytotoxicity through the upregulation of Grb2 expression and the activation of MAPK signal transduction in the HepG2 cell line.
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Copy and paste a formatted citation
Spandidos Publications style
Gui R, Li D, Qi G, Suhad A and Nie X: Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line. Oncol Lett 4: 566-570, 2012.
APA
Gui, R., Li, D., Qi, G., Suhad, A., & Nie, X. (2012). Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line. Oncology Letters, 4, 566-570. https://doi.org/10.3892/ol.2012.774
MLA
Gui, R., Li, D., Qi, G., Suhad, A., Nie, X."Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line". Oncology Letters 4.3 (2012): 566-570.
Chicago
Gui, R., Li, D., Qi, G., Suhad, A., Nie, X."Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line". Oncology Letters 4, no. 3 (2012): 566-570. https://doi.org/10.3892/ol.2012.774
Copy and paste a formatted citation
x
Spandidos Publications style
Gui R, Li D, Qi G, Suhad A and Nie X: Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line. Oncol Lett 4: 566-570, 2012.
APA
Gui, R., Li, D., Qi, G., Suhad, A., & Nie, X. (2012). Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line. Oncology Letters, 4, 566-570. https://doi.org/10.3892/ol.2012.774
MLA
Gui, R., Li, D., Qi, G., Suhad, A., Nie, X."Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line". Oncology Letters 4.3 (2012): 566-570.
Chicago
Gui, R., Li, D., Qi, G., Suhad, A., Nie, X."Inhibition of Grb2‑mediated activation of MAPK signal transduction suppresses NOR1/CB1954‑induced cytotoxicity in the HepG2 cell line". Oncology Letters 4, no. 3 (2012): 566-570. https://doi.org/10.3892/ol.2012.774
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