Guangdong Province Key Laboratory of Molecular Immunology and Antibody Engineering, Biomedicine Translational Institute, Jinan University, Guangzhou, Guangdong 510640, P.R. China.
Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94122, USA.
Mol Med Rep. 2017 Oct;16(4):4015-4021. doi: 10.3892/mmr.2017.7099. Epub 2017 Jul 27.
Basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor 1 (FGFR1) are associated with drug resistance in lung cancer. In the present study, mouse monoclonal antibodies (mAb) against human bFGF, targeting the binding site of bFGF with FGFR1 were produced, and the antitumor activity and inhibition of metastasis was studied in Lewis lung carcinoma (LLC). A total of four hybridoma cell strains that stably secreted bFGF mAb were obtained. mAbE12 was selected as the most effective for use in the following studies, with a relative affinity constant of 5.66x108 l/mol. mAbE12 was demonstrated to inhibit cell proliferation and tumor growth in vitro and in vivo. Furthermore, mAbE12 blocked migration and metastasis of LLC cells in vitro and in vivo. This occurred due to a mAbE12‑induced upregulation of E‑cadherin expression through the protein kinase B‑glycogen synthase kinase 3 β‑Snail pathway. These results suggested that mAbE12 may be a potential antibody for the treatment of lung cancer.
碱性成纤维细胞生长因子（bFGF）和成纤维细胞生长因子受体 1（FGFR1）与肺癌的耐药性有关。在本研究中，制备了针对 bFGF 与 FGFR1 结合位点的人 bFGF 单克隆抗体（mAb），并研究了其在 Lewis 肺癌（LLC）中的抗肿瘤活性和抑制转移作用。获得了 4 株稳定分泌 bFGF mAb 的杂交瘤细胞株。选择 mAbE12 作为进一步研究的最有效抗体，其相对亲和常数为 5.66x108 l/mol。mAbE12 被证明可抑制 LLC 细胞的体外和体内增殖和肿瘤生长。此外，mAbE12 可阻断 LLC 细胞的体外和体内迁移和转移。这是由于 mAbE12 通过蛋白激酶 B-糖原合成酶激酶 3β-Snail 通路诱导 E-钙黏蛋白表达上调所致。这些结果表明，mAbE12 可能是治疗肺癌的一种有潜力的抗体。
