TY - JOUR AB - 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. AD - Cancer Research Institute, Catholic Research Institutes of Medical Sciences, The Catholic University of Korea, Seoul 137-701, Korea null AU - Kang,Byoung-Hak AU - Shim,Byoung-Shik AU - Lee,Soo,Young AU - Lee,Suk-Keun AU - Hong,Yong-Kil AU - Joe,Young,Ae DA - 2006/02/01 DO - 10.3892/ijo.28.2.361 EP - 367 IS - 2 JO - Int J Oncol PY - 2006 SN - 1019-6439 1791-2423 SP - 361 ST - Potent anti-tumor and prolonged survival effects of E. coli-derived non-glycosylated kringle domain of tissue-type plasminogen activator T2 - International Journal of Oncology TI - Potent anti-tumor and prolonged survival effects of E. coli-derived non-glycosylated kringle domain of tissue-type plasminogen activator UR - https://doi.org/10.3892/ijo.28.2.361 VL - 28 ER -