Extended Data Fig. 7: Chidamide potentiates the actions of TKIs against HCC cells.
a-b, Cell viability measurements in HCCLM3 (a) and MHCC-97H (b) cells over 24–72 h after treatment with the indicated concentrations of donafenib and chidamide. n = 4 biological replicates. c, Colony formation assays conducted in MHCC-97H cells treated with donafenib, chidamide and chidamide plus donafenib. Images are representative of n = 3 independent experiments. d-f, Cell viability of MHCC-97H cells over 24–72 h after treatment with chidamide alone or in combination with lenvatinib (d), sorafenib (e) and regorafenib (f). n = 4 biological replicates. g–i, Cell viability of HCCLM3 cells over 24–72 h after treatment with chidamide alone or in combination with lenvatinib (g), sorafenib (h) and regorafenib (i). n = 4 biological replicates. j–l, Colony formation assays conducted in HCCLM3 cells treated with vehicle control (DMSO) or 2.5 μM chidamide in combination with the indicated concentrations of lenvatinib (j), sorafenib (k), and regorafenib (l). Images are representative of n = 3 independent experiments. m-o, The drug combination index analysis of Chidamide and donafenib (m), Chidamide and sorafenib (n), Chidamide and Lenvatinib (o). p, Representative HE images of patient-derived organoids derived from HCC tissues(n = 3 independent experiments). q. Schematic representing the development of the HCC PDX models in NSG-nude mice and experimental treatment schemes using chidamide or combining chidamide and donafenib. r-s, The ki67 IHC staining (r) and quantification (s) of HCC tumors treated with donafenib, chidamide and the combination treatment. in various liver tissues (n = 3 mice/group). t, Schematic depicting the autologous Hep1-6 HCC tumor model in C57/BL mice. u. Experimental scheme for implementing the SgP53/Myc spontaneous liver tumor model with the primary measure of survival data. v-w, Quantification of animal body weights during treatment in the PDX/NSG (n = 5 mice/group; v) and Hep1-6/C57/BL (n = 6 mice/group; w) murine tumor models (related to Fig. 7q and s, respectively). Data were analyzed by one-way ANOVA with Tukey’s multiple comparisons test (s) and two-way ANOVA with Tukey’s multiple comparisons test (v and w). All quantitative data are represented as mean ± SD. All microscopy images are representative of n = 3 independent experiments.
