I131 reinforces antitumor activity of metuximab by reversing epithelial–mesenchymal transition via VEGFR‐2 signaling in hepatocellular carcinoma. (6th December 2017)

• Record Type: Journal Article
• Authors: Wu, Lu; Sun, Bin; Lin, Xuejing; Liu, Chunying; Qian, Haihua; Chen, Lei; Yang, Yefa; Shen, Feng; Su, Changqing
• Is Part Of: Genes to cells. Volume 23:Number 1(2018)
• Page Start: 35
• Page End: 45
• Publication Date: 2017-12-06
• Subjects: CD147 -- epithelial–mesenchymal transition -- hepatocellular carcinoma -- radio‐immunotherapy -- VEGFR‐2 signaling pathway; Cytogenetics -- Periodicals; Cells -- Mechanical properties -- Periodicals; Molecular genetics -- Periodicals; Genes -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Biomechanics -- Periodicals; 571.6
• DOI: 10.1111/gtc.12545
• Languages: English
• ISSNs: 1356-9597

Abstract

Abstract : CD147 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 CD147, 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 CD147‐mab and consequently reinforced the anticancer effects of CD147‐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 CD147‐mab significantly inhibited the growth of xenograft tumors and that I 131 ‐mab was more effective than CD147‐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. Abstract : I 131 ‐mab exerts a synergistic anticancer activity against HCC. I 131 ‐mab could reverse epithelial–mesenchymal transition of HCC cells partially by suppressing the VEGFR‐2 pathway.