Figure 4.

Gemcitabine treatment induces p53-mediated cell death, through SIRT1 depletion in ATRT

(A) Western blot analysis depicting SIRT1 expression in VUMC-ATRT-01 and VUMC-ATRT-03 cells transduced with a variety of SIRT1 shRNA (Sh#1, 2, and 3) or a control construct (wild type [WT]).

(B) IC50 viability curves of VUMC-ATRT-01 and VUMC-ATRT-03 cells transduced with control (scrambled) or one of three SIRT1 shRNA treated with different gemcitabine concentrations for 96 h.

(C) Western blot analysis depicting p53 expression in VUMC-ATRT-01 WT and p53 knockout cells (KO1 and KO2), as established through CRISPR-Cas9.

(D) IC50 viability curves of CRISPR-Cas9-modified VUMC-ATRT-01 WT, scrambled, and p53 knockout cells, treated with different gemcitabine concentration for 96 h.

(E) Illustration of the proposed mechanism through which gemcitabine causes tumor toxicity in ATRT.