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. 2020 Mar 23;122(10):1486–1495. doi: 10.1038/s41416-020-0782-1

Fig. 3. Effects of HGF/c-MET inhibition ± gemcitabine on cancer cell proliferation and apoptosis.

Fig. 3

a Representative photomicrographs of immunostaining for PCNA (brown nuclear staining). Scale bars = 50 µm. The negative control for PCNA staining (sections stained with equivalent concentration of isotype IgG) is shown in Supplementary Fig. 8a. b Effects of HGF/c-MET inhibition ± gemcitabine on cancer cell proliferation. Treatment with gemcitabine (G), HGF-neutralising antibody + gemcitabine (Hi + G), c-MET inhibitor + gemcitabine (Ci + G) or triple therapy (Hi + Ci + G) significantly reduced PCNA-positive cells (proliferating cells) in the tumours. ***p < 0.001, Hi + Ci + G vs. IgG, Hi or Ci; **p < 0.01, G vs. IgG; *p < 0.05 Ci + G vs. IgG; #p < 0.05, Hi + G vs. IgG or Hi; n = 6 mice per group. c Representative photomicrographs of TUNEL staining (blue nuclear staining). Scale bars = 50 µm. The negative control and positive control for TUNEL staining are shown in Supplementary Fig. 8b, c, respectively. d Effects of HGF/c-MET inhibition ± gemcitabine on cancer cell apoptosis. The apoptotic cancer cell density in gemcitabine (G)-treated tumours showed a trend towards an increase compared to those treated with IgG (p = 0.096). Triple therapy (Hi + Ci + G) significantly induced cancer cell apoptosis in tumours compared to tumours in the IgG, HGF-neutralising antibody (Hi) and HGF-neutralising antibody + c-MET inhibitor (Hi + Ci) groups. HGF-neutralising antibody + gemcitabine (Hi + G) and c-MET inhibitor + gemcitabine (Ci + G) also significantly increased cancer cell apoptosis compared to IgG and Hi groups. **p < 0.01, Hi + Ci + G vs. IgG or Hi; *p < 0.05, Hi + Ci + G vs. Hi + Ci; #p < 0.05, Hi + G or Ci + G vs. IgG or Hi; n = 6 mice per group.