Fig. 6

Combination shikonin and doxorubicin reprograms TACE response in patient derived organoids. (a) 33 HCC patient derived cells lines were screened for relative mRNA expression of PKM2. Two representative cell lines were selected from PKM2 high lines and two representative PKM2 low lines for downstream analysis. (b) Organoid viability was measured after 72 h of treatment with doxorubicin with or without shikonin in addition to subjection of acute hypoxia. PKM2 low lines exhibited decreased viability with doxorubicin alone whereas PKM2 high lines demonstrated resistance to doxorubicin which could be overcome with the combination of doxorubicin and shikonin (c) Relative change in doxorubicin and shikonin response as compared to doxorubicin alone demonstrating decreased viability with the combination of shikonin and doxorubicin in all line lines. (d) Histology of patient derived organoid before treatment and after combination doxorubicin and shikonin treatment in hypoxia