I 131 reinforces antitumor activity of metuximab by reversing epithelial–mesenchymal transition via VEGFR ‐2 signaling in hepatocellular carcinoma

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.