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I 131 reinforces antitumor activity of metuximab by reversing epithelial–mesenchymal transition via VEGFR ‐2 signaling in hepatocellular carcinoma
Author(s) -
Wu Lu,
Sun Bin,
Lin Xuejing,
Liu Chunying,
Qian Haihua,
Chen Lei,
Yang Yefa,
Shen Feng,
Su Changqing
Publication year - 2018
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/gtc.12545
Subject(s) - monoclonal antibody , hepatocellular carcinoma , cancer research , epithelial–mesenchymal transition , biology , antibody , metastasis , immunotherapy , mesenchymal stem cell , cancer , immunology , microbiology and biotechnology , immune system , genetics
CD 147 is highly expressed in hepatocellular carcinoma ( HCC ) and associated with the invasion and metastasis of HCC . The efficacy of I 131 ‐metuximab (I 131 ‐mab), a newly developed agent that targets CD 147, as a radio‐immunotherapy for local HCC , has been validated in clinical practice. However, the synergistic anticancer activity and molecular mechanism of different conjugated components within I 131 ‐mab remain unclear. In this study, the cytological experiments proved that I 131 ‐mab inhibited the proliferation and invasion of HCC cells. Mechanically, this inhibition effect was mainly mediated by the antibody component part of I 131 ‐mab, which could reverse the epithelial–mesenchymal transition of HCC cells partially by suppressing the phosphorylation of VEGFR ‐2. The inhibitory effect of I 131 on HCC cell proliferation and invasion is limited, whereas, when combined with metuximab, I 131 significantly enhanced the sensitivity of HCC cells to CD 147‐mab and consequently reinforced the anticancer effects of CD 147‐mab, suggesting that the two components of I 131 ‐mab exerted synergistic anti‐ HCC capability. Furthermore, the experiments using SMMC ‐7721 human HCC xenografts in athymic nude mice showed that I 131 ‐mab and CD 147‐mab significantly inhibited the growth of xenograft tumors and that I 131 ‐mab was more effective than CD 147‐mab. In conclusion, our results elucidated the mechanism underlying the anti‐ HCC effects of I 131 ‐mab and provided a theoretical foundation for the clinical application of I 131 ‐mab.