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

Zhong,Gen-Shen; Wu,Min-Na; Guo,Xiao-Fang; Zhang,Sheng-Hua; Miao,Qing-Fang; Zhen,Yong-Su

doi:10.3892/or.2012.1910

October 2012 Volume 28 Issue 4

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October 2012 Volume 28 Issue 4

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Article

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
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Affiliations: The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, Henan Province 453100, P.R. China, Xinxiang Medical University, Xinxiang, Henan Province 453003, P.R. China, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China
Pages: 1193-1199
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Published online on: July 13, 2012

https://doi.org/10.3892/or.2012.1910
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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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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

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

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