Panoply™ Human FGFR1 Over-expressing Stable Cell Line

Hepatocellular carcinoma (HCC) is a highly aggressive solid tumor with limited treatment options. Lenvatinib is currently the second approved first-line drug for the treatment of advanced HCC, but cases of lenvatinib resistance have been reported clinically. Overexpression of fibroblast growth factor receptor 1 (FGFR1) is closely associated with advanced HCC. Here, researchers found that FGFR1 overexpression and activation of its downstream AKT/mTOR and ERK signaling pathways can induce lenvatinib resistance in HCC cells. In vivo and in vitro experimental results showed that Oxysophocarpine can inhibit the proliferation of FGFR1-overexpressing HCC cells and induce their apoptosis. Oxysophocarpine can further enhance the sensitivity of FGFR1-overexpressing HCC cells to lenvatinib. Mechanistic studies showed that Oxysophocarpine enhances the sensitivity of FGFR1-overexpressing HCC cells to lenvatinib by downregulating FGFR1 expression and downstream AKT/mTOR and ERK signaling pathways. These data collectively suggest that FGFR1 overexpression may be a potential cause of lenvatinib resistance, and that Oxysophocarpine may be an ideal drug to be used in combination with lenvatinib for the treatment of HCC.

To investigate whether Oxysophocarpine could rescue the sensitivity of FGFR1-overexpressing hepatocellular carcinoma cells to lenvatinib, researchers treated FGFR1-overexpressing Hep3B and HepG2 cells with 10 μM Oxysophocarpine in combination with 5 μM lenvatinib. In cell proliferation assays, Oxysophocarpine combined with lenvatinib exerted the most suppressive influence on the cell proliferation compare to control or alone treatment (Figure 1A). In colony formation assays, the combination significantly inhibited colony formation in FGFR1-overexpressing Hep3B and HepG2 cells compared to either Oxysophocarpine or lenvatinib alone (Figure 1B and C). They also investigated the effect of the combination on the migration of FGFR1-overexpressing hepatocellular carcinoma cells. FGFR1-overexpressed Hep3B and HepG2 cells were previously treated with 10 μM Oxysophocarpine combined with 5 μM lenvatinib for 24 h. Oxysophocarpine combined with lenvatinib evidently inhibited the migration of FGFR1-overexpressed Hep3B and HepG2 cells (Figure 1D and E). In summary, the researchers hypothesize that Oxysophocarpine enhances the sensitivity of FGFR1-overexpressing Hep3B and HepG2 cells to lenvatinib in vitro.

Figure 1. Oxysophocarpine sensitized FGFR1-overexpressed Hep3B and HepG2 cells to lenvatinib in vitro. (Zhao Z, et al., 2021)