fig6

Figure 6. Silencing LINC01607 enhances sorafenib sensitivity in cellular, animal, and PDO models. (A) Cell viability assays (CCK-8) in Hep3B and Huh7 cells were conducted to evaluate sorafenib sensitivity under conditions of LINC01607 knockdown or overexpression. Knockdown of LINC01607 significantly reduced the IC50 of sorafenib, while overexpression increased the IC50, indicating enhanced drug resistance; (B) CCK-8 assays were used to assess RSL3 sensitivity in Hep3B and Huh7 cells with LINC01607 knockdown or overexpression; (C) Ferrostatin-1 rescue assays under sorafenib treatment were performed to determine whether ferroptosis contributed to the increased sorafenib sensitivity induced by LINC01607 knockdown; (D) Subcutaneous xenograft experiments in nude mice revealed that LINC01607 knockdown sensitized tumors to sorafenib. The combination of sh-LINC01607 and sorafenib produced a greater reduction in tumor growth and tumor weight than either treatment alone; (E) H&E and IHC staining were performed to assess the expression of p62, KEAP1, NRF2, GPX4, and HO-1 in subcutaneous xenografts; (F) CCK-8 assays were used to determine cell viability in six organoid models, and organoid viability exhibited a positive correlation with LINC01607 expression levels; (G) Bright-field images of patient-derived HCC organoids treated with sorafenib, LINC01607 silencing, or their combination for four days. LINC01607 silencing and sorafenib synergistically reduced organoid diameter and cell viability. Quantifications of organoid diameters and cell viability are shown in the right panels. Data are presented as mean ± SD. For cell-based drug-sensitivity assays, n = 3 independent biological replicates unless otherwise indicated. For xenograft experiments, n = 6 mice per group. For PDO analyses, n = 6 independent PDO lines for the correlation analysis, and organoid treatment assays were performed in three independent experimental replicates unless otherwise indicated. ^*P < 0.05, ^**P < 0.01, ^***P < 0.001. PDO: Patient-derived organoid; CCK-8: Cell Counting Kit-8; H&E: hematoxylin and eosin; IHC: immunohistochemistry; SD: standard deviation.