Figure 1

Development of a hepatoblastoma cisplatin-resistant xenograft model. (A) Human hepatoblastoma cells, HuH6, or hepatoblastoma patient-derived xenografts, COA67, were injected or implanted, subcutaneously, into the flank of one female athymic nude mouse each. Once tumor volume reached 100 mm³ for HuH6 and 300 mm³ for COA67, the animal was treated with cisplatin via intraperitoneal injection (2 mg/kg/day for 3 consecutive days weekly for HuH6 and 1 mg/kg/day for 2 consecutive days weekly for COA67). Tumors were harvested to yield “cisplatin-resistant” cells, which were used for studies, and serially passed into a second mouse. Alternatively, tumors from mice not treated with cisplatin were utilized as controls, yielding “cisplatin-naïve” HuH6 and COA67 cells. (B–E) Cisplatin-resistant and cisplatin-naïve cells were treated with cisplatin at increasing concentrations (0 to 30 µM) for 72 h, and cell proliferation and viability were measured with CellTiter 96 and alamarBlue assays, respectively. (B,D) Proliferation and (C,E) viability was less affected given the same dose of cisplatin in resistant compared to naïve cells. The IC₅₀ and LD₅₀ values were calculated following treatment with cisplatin. Resistant cells had a higher IC₅₀ and higher LD₅₀ compared to naïve cells. These findings confirmed the cisplatin resistance model in both HuH6 and COA67 hepatoblastoma xenografts. Data reported as mean ± SEM.