I reinforces antitumor activity of metuximab by reversing epithelial-mesenchymal transition via VEGFR-2 signaling in hepatocellular carcinoma.

CD147 is highly expressed in hepatocellular carcinoma (HCC) and associated with the invasion and metastasis of HCC. The efficacy of I -metuximab (I -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 -mab remain unclear. In this study, the cytological experiments proved that I -mab inhibited the proliferation and invasion of HCC cells. Mechanically, this inhibition effect was mainly mediated by the antibody component part of I -mab, which could reverse the epithelial-mesenchymal transition of HCC cells partially by suppressing the phosphorylation of VEGFR-2. The inhibitory effect of I on HCC cell proliferation and invasion is limited, whereas, when combined with metuximab, I 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 -mab exerted synergistic anti-HCC capability. Furthermore, the experiments using SMMC-7721 human HCC xenografts in athymic nude mice showed that I -mab and CD147-mab significantly inhibited the growth of xenograft tumors and that I -mab was more effective than CD147-mab. In conclusion, our results elucidated the mechanism underlying the anti-HCC effects of I -mab and provided a theoretical foundation for the clinical application of I -mab.