Potent anti-tumor and prolonged survival effects of E. coli-derived non-glycosylated kringle domain of tissue-type plasminogen activator

  • Authors:
    • Byoung-Hak Kang
    • Byoung-Shik Shim
    • Soo Young Lee
    • Suk-Keun Lee
    • Yong-Kil Hong
    • Young Ae Joe
  • View Affiliations

  • Published online on: February 1, 2006     https://doi.org/10.3892/ijo.28.2.361
  • Pages: 361-367
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Abstract

The two-kringle domain of tissue-type plasminogen activator (TK1-2) has been identified as a novel angiogenesis inhibitor. In the previous study, purified Pichia-derived TK1-2 has been shown to suppress in vivo growth of human lung and colon cancer cells. Here, we demonstrate that E. coli-derived non-glycosylated TK1-2 suppresses tumor growth more potently than Pichia-derived TK1-2 and prolongs the survival of tumor bearing mice. The recombinant TK1-2 prepared through E. coli expression, His-tag affinity chromatography and in vitro refolding was injected intraperitoneally once daily into nude mice 7 days after subcutaneous implantation with PC14 lung cancer cells (n=10). Measurement of tumor volumes indicated that low-dose TK1-2 treatment (10 mg/kg) suppressed tumor growth by approximately 85.2% (p<0.01), while high-dose TK1-2 treatment (50 mg/kg) even more potently inhibited tumor growth (>93.8%) (p<0.005). Treatment of TK1-2 also prolonged the survival of tumor-bearing mice in a dose-dependent fashion. In an independent HCT116 xenograft model, E. coli-derived TK1-2 was more effective in suppressing tumor growth than Pichia-derived TK1-2. Immunohistochemical analysis of tumor tissue also revealed that the expression of VEGF, SMA-α, TNF-α and angiogenin was less positive in the E. coli-derived TK1-2-treated group than in the Pichia-derived TK1-2-treated group. These results suggest that E. coli-derived refolded, non-glycosylated TK1-2 can be used more effectively as an anti-cancer agent.

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February 2006
Volume 28 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Kang B, Shim B, Lee SY, Lee S, Hong Y and Joe YA: Potent anti-tumor and prolonged survival effects of E. coli-derived non-glycosylated kringle domain of tissue-type plasminogen activator. Int J Oncol 28: 361-367, 2006
APA
Kang, B., Shim, B., Lee, S.Y., Lee, S., Hong, Y., & Joe, Y.A. (2006). Potent anti-tumor and prolonged survival effects of E. coli-derived non-glycosylated kringle domain of tissue-type plasminogen activator. International Journal of Oncology, 28, 361-367. https://doi.org/10.3892/ijo.28.2.361
MLA
Kang, B., Shim, B., Lee, S. Y., Lee, S., Hong, Y., Joe, Y. A."Potent anti-tumor and prolonged survival effects of E. coli-derived non-glycosylated kringle domain of tissue-type plasminogen activator". International Journal of Oncology 28.2 (2006): 361-367.
Chicago
Kang, B., Shim, B., Lee, S. Y., Lee, S., Hong, Y., Joe, Y. A."Potent anti-tumor and prolonged survival effects of E. coli-derived non-glycosylated kringle domain of tissue-type plasminogen activator". International Journal of Oncology 28, no. 2 (2006): 361-367. https://doi.org/10.3892/ijo.28.2.361