Inhibition activity of a disulfide-stabilized diabody against basic fibroblast growth factor in lung cancer
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Yaxiong Cai1,*, Shuange Yao1,*, Jiangchuan Zhong1,*, Jinxia Zhang1, Haowu Jiang1, Yanrui Deng1, Ning Deng1
1Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, College of Bioscience and Technology in Jinan University, Guangzhou, China
*These authors have contributed equally to this work
Ning Deng, email: [email protected]
Keywords: ds-diabody, bFGF, lung cancer, angiogenesis, lymphangiogenesis
Received: July 29, 2016 Accepted: January 23, 2017 Published: February 21, 2017
The over-expression of basic fibroblast growth factor (bFGF) plays a crucial role in the development, invasion and metastasis of lung cancer. Therefore, neutralizing antibodies against bFGF may inhibit the growth of lung cancer. In this study, a Disulfide-stabilized diabody (ds-Diabody) against bFGF was constructed by site-directed mutation and overlap extension PCR (SOE-PCR) at the position of VH44 and VL100 in the scFv. The ds-Diabody was constructed and expressed in Pichia pastoris. We found that the ds-Diabody against bFGF could efficiently suppress the proliferation, migration and invasion of human lung cancer A549 cells in vitro. Moreover, in A549 cells, the ds-Diabody against bFGF could inhibit bFGF-induced activation of downstream signaling regulators, such as phospho-Akt and phospho-MAPK. In the nude mouse xenograft model of lung cancer, the ds-Diabody against bFGF could significantly inhibit tumor growth and decrease the densities of micro-vessels and lymphatic vessels in tumor tissue. Our data indicate that the ds-Diabody against bFGF could effectively suppress the lung cancer growth through blockade of bFGF signaling pathway and inhibition of tumor angiogenesis, which may make it a potential therapeutic candidate antibody drug for human lung cancer therapy.
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