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Article

Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2

  • Authors:
    • Xin Shao
    • Hui Ren
    • Yue-Li Wang
    • Fa Wang
    • Gan Hou
    • Di-Nan Huang
  • View Affiliations / Copyright

    Affiliations: Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, Guangdong 524023, P.R. China, Department of Clinical Biochemistry, Guangdong Medical College, Dongguan, Guangdong 523808, P.R. China
  • Pages: 810-818
    |
    Published online on: November 24, 2014
       https://doi.org/10.3892/or.2014.3616
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Abstract

The aim of this study was to examine the tumor therapy, targeting effects and side effects of tumor‑targeting rhTNF-α fusion protein mediated by matrix metalloproteinase-2 in an animal model in order to provide experimental data for future development of drugs. The median lethal dose (LD50) was obtained from acute toxicity experiments. The A549 lung cancer xenograft model was established, and then randomly divided into the saline, standard substance, and low‑, middle‑ and high‑dose fusion protein experiment groups. Each group was administered drugs for 18 days. The length and width of the xenografts were measured every three days, after which the xenograft growth curve was drawn. The mice were sacrificed in each group following treatment and the tumor volume and weight were measured. The targeting, effectiveness and toxicity of the transformed fusion protein, and pathological changes of tumor and organ tissues were examined by hematoxylin and eosin (H&E) staining. Additionally, biochemical markers were used to detect damage of various organs after protein processing. Cell apoptosis and angiogenesis were determined using terminal deoxynucleotidyltransferase-mediated dUTP nick end‑labeling (TUNEL) testing and immunohistochemistry, respectively, in different dose groups. Tumor growth was markedly retarded in the high‑dose experimental and standard hTNF-α groups with antitumor rates of 85.91 and 72.25%, respectively, as compared with the control group. Furthermore, the tumor tissue showed obvious apoptosis (the apoptotic index was 78.78 and 66.65%, respectively) and pathological changes in the high‑dose experimental and standard hTNF-α groups. Tumor angiogenesis in each fusion protein group was inhibited (P<0.01) and the biochemical markers of various organs were greatly reduced in the high‑dose experimental group (P<0.05). This finding indicated that slight toxic effects of fusion proteins were evident for the heart, liver and kidney. The reforming fusion protein can therefore target tumor tissues and efficiently kill tumor cells, with few side effects.
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Copy and paste a formatted citation
Spandidos Publications style
Shao X, Ren H, Wang Y, Wang F, Hou G and Huang D: Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2. Oncol Rep 33: 810-818, 2015.
APA
Shao, X., Ren, H., Wang, Y., Wang, F., Hou, G., & Huang, D. (2015). Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2. Oncology Reports, 33, 810-818. https://doi.org/10.3892/or.2014.3616
MLA
Shao, X., Ren, H., Wang, Y., Wang, F., Hou, G., Huang, D."Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2". Oncology Reports 33.2 (2015): 810-818.
Chicago
Shao, X., Ren, H., Wang, Y., Wang, F., Hou, G., Huang, D."Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2". Oncology Reports 33, no. 2 (2015): 810-818. https://doi.org/10.3892/or.2014.3616
Copy and paste a formatted citation
x
Spandidos Publications style
Shao X, Ren H, Wang Y, Wang F, Hou G and Huang D: Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2. Oncol Rep 33: 810-818, 2015.
APA
Shao, X., Ren, H., Wang, Y., Wang, F., Hou, G., & Huang, D. (2015). Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2. Oncology Reports, 33, 810-818. https://doi.org/10.3892/or.2014.3616
MLA
Shao, X., Ren, H., Wang, Y., Wang, F., Hou, G., Huang, D."Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2". Oncology Reports 33.2 (2015): 810-818.
Chicago
Shao, X., Ren, H., Wang, Y., Wang, F., Hou, G., Huang, D."Targeting antitumor effect of rhTNF-α fusion protein mediated by matrix metalloproteinase-2". Oncology Reports 33, no. 2 (2015): 810-818. https://doi.org/10.3892/or.2014.3616
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