Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases

  • Authors:
    • Gen-Shen Zhong
    • Min-Na Wu
    • Xiao-Fang Guo
    • Sheng-Hua Zhang
    • Qing-Fang Miao
    • Yong-Su Zhen
  • View Affiliations

  • Published online on: July 13, 2012     https://doi.org/10.3892/or.2012.1910
  • Pages: 1193-1199
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Abstract

Gelatinases play an important role in tumor growth and metastasis, and overexpression of these molecules is strongly correlated with poor prognosis in a variety of malignant tumors. Lidamycin is an enediyne antitumor antibiotic with potent cytotoxicity. We previously reported that a tandem scFv format (dFv-LDP-AE) showed enhanced binding ability with gelatinases compared with the scFv-lidamycin conjugate (Fv-LDP-AE). In this study, the antitumor activities of dFv-LDP-AE on hepatocellular carcinoma (HCC) were evaluated in vitro and in vivo. By SDS-PAGE analysis, it was found that partial fusion protein dFv-LDP existed as dimer; the results of ELISA and immunofluorescence demonstrated that the fusion protein dFv-LDP could efficiently bind to hepatoma cells in vitro. The apparent arrest of cell cycle at G2/M phase and induction of apoptosis at nanomole levels indicated that the dFv-LDP-AE was very potent against HCC. In in vivo experiments, dFv-LDP-AE shown enhanced cytotoxic effects compared to those of LDM. Administration at mouse tolerable dosage level, the inhibition rate of tumor growth was 89.5% of dFv-LDP-AE vs. 73.6% of LDM on transplantable H22 in mice (P<0.05) and, 87.3% of dFv-LDP-AE vs. 63.4% of LDM on hepatoma Bel-7402 in athymic mice (P<0.01). Small animal optical imaging showed that the FITC-labeled dFv-LDP preferentially localized in the tumor site in less than 30 min, which demonstrated remarkable tumor-targeting properties. Taken together with the above findings, the enediyne-energized fusion protein dFv-LDP-AE showed potential application as a new agent for therapeutic appications in HCC.
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October 2012
Volume 28 Issue 4

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

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Spandidos Publications style
Zhong G, Wu M, Guo X, Zhang S, Miao Q and Zhen Y: Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases. Oncol Rep 28: 1193-1199, 2012
APA
Zhong, G., Wu, M., Guo, X., Zhang, S., Miao, Q., & Zhen, Y. (2012). Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases. Oncology Reports, 28, 1193-1199. https://doi.org/10.3892/or.2012.1910
MLA
Zhong, G., Wu, M., Guo, X., Zhang, S., Miao, Q., Zhen, Y."Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases". Oncology Reports 28.4 (2012): 1193-1199.
Chicago
Zhong, G., Wu, M., Guo, X., Zhang, S., Miao, Q., Zhen, Y."Antitumor activities of dFv-LDP-AE: An enediyne-energized fusion protein targeting tumor-associated antigen gelatinases". Oncology Reports 28, no. 4 (2012): 1193-1199. https://doi.org/10.3892/or.2012.1910