Fig. 6

Pharmacological VC impairs tumor growth and preferentially kills liver CSCs in vivo, and intravenous VC reduces the risk of post-surgical HCC progression. a Huh7 cells were subcutaneously inoculated into nude mice. When tumors grew to ~50 mm³, treatment commenced with intraperitoneal injection of VC (4 g/kg, twice every day) and cisplatin (Cp; 3 mg/kg, twice per week) either alone or in combination. Tumor sizes were measured twice per week. After ~21 days of treatment, mice were euthanized and total tumor weights were measured. b Western blot analysis showing stemness and apoptotic markers expressions in tumor xenograft after treatment of VC and cisplatin either alone or in combination. Samples derived from the same experiment and gels/blots were processed in parallel. c IHC analysis showing stemness and apoptotic markers expressions in tumor xenograft after treatment of VC and cisplatin either alone or in combination. Scale bars = 100 μm. d IHC analysis showing SVCT-2 expression between PDXs from patient #1, #2, and #3. Scale bars = 100 μm. e Relative weights of PDXs from patient #1, #2, and #3 after ~21 days of VC treatment. PDXs were treated intraperitoneally twice daily with either VC (4.0 g/kg) or vehicle (PBS). f qRT-PCR analysis for stemness markers in PDXs from patient #1 and #3 after treatment of either VC or vehicle (PBS). g IHC analysis showing Oct-4, CD133, and Lin28 expressions in PDXs from patient #1 and #3 after treatment of either VC or vehicle (PBS). Scale bars = 100 μm. h DFS of 613 patients with primary HCC after initial hepatectomy receiving 2 g intravenous VC, or not. i Schematic showing how VC kills cancer cells and preferentially kills CSCs via SVCT-2. Data are representative of at least three independent experiments and shown as mean ± s.d. (*p < 0.05; **p < 0.01; ***p < 0.001)