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Fig. 6 | Journal of Experimental & Clinical Cancer Research

Fig. 6

From: Macropinocytosis is an alternative pathway of cysteine acquisition and mitigates sorafenib-induced ferroptosis in hepatocellular carcinoma

Fig. 6

Sorafenib-resistant HCC cells show enhanced macropinocytosis, and amiloride sensitizes resistant HCC tumors to sorafenib. A Relative numbers of Huh7 and SK-Hep1 (sorafenib-sensitive, SS) and sorafenib-resistant Huh7 and SK-Hep1 (sorafenib-resistant, SR) cells treated with sorafenib for 24 h. B Levels of phosphorylated PAK1 in Huh7 (SS and SR) and SK-Hep1 (SS and SR) cells. C and D Representative images of macropinosomes (red; C) and DQ-BSA fluorescence (green; D) in sorafenib-resistant Huh7 (SR) and SK-Hep1 (SR) in the presence or absence of EIPA or amiloride (scale bar, 20 µm). E Growth curve of Huh7 (SR)-xenografted tumors after drug treatment. F H&E staining (scale bar, 150 µm) and immunofluorescence staining of tumor tissues with anti-4-HNE (scale bar, 20 µm). Hashed lines indicate regional necrosis (N). (G) Schematic showing the role of macropinocytosis in sorafenib resistance: macropinocytosis mitigates sorafenib-induced ferroptosis in HCC. Data are normalized against values measured in vehicle-treated cells (SS-Veh) or tumors (Con), and expressed as the mean ± SEM of at least three independent experiments, or from independent xenografts (n = 3–4 per group). N.S., not significant; *p < 0.05 and *** p < 0.001

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