Fig. 8: Proof-of-concept for therapeutic impact of nizatidine in patient-derived tissues and cell culture models. | Nature Communications

Fig. 8: Proof-of-concept for therapeutic impact of nizatidine in patient-derived tissues and cell culture models.

From: A human liver cell-based system modeling a clinical prognostic liver signature for therapeutic discovery

Fig. 8

a Nizatidine reverts the poor-prognosis PLS in culture of patient-derived tissue that were surgically resected from five patients diagnosed with chronic hepatitis C (HCV). Detailed PLS gene expression profiles: heatmaps show the mean expression of the 186 gene signature. PLS was determined by GSEA analysis using DMSO treated tissues as reference. Simplified heatmaps show: (top) the classification of PLS status as poor (orange) or good (green) prognosis; (bottom) the significance of induction (red) or suppression (blue) of poor- or good-prognosis genes. FDR false discovery rate. b Absent effect on cell viability in PHH, assessed 4 days after nizatidine treatment in 3D culture. Each experiment shows mean ± SD in percentage compared to DMSO treated cells (n = 4). c Nizatidine decreases HCC cell viability in a 3D patient-derived tumorspheroid model. HCC spheroids were generated from patient HCC tissues with different etiologies. Cell viability was assessed 4 days after treatment by measuring ATP levels. Each experiment shows mean ± SD in percentage compared to DMSO treated spheroids (n = 4). *p < 0.05; **p < 0.01, unpaired t test. The pictures show representative image of patient-derived tumorspheroids (magnification ×40). NASH nonalcoholic steatohepatitis, ALD alcoholic liver disease. Source data are provided as a Source data file.

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