(A) CRISPR/cas9n-mediated deletion of PKR promotes Taxol resistance. Two independent guide RNAs (KO-1 and KO-2) were used in each cell line. Cells were treated with Taxol (100 nM) for 24 h and total cell lysates were probed with the indicated antibodies. Cleaved (Cl)-PARP serves as an apoptotic marker.
(B) Cells were incubated with Taxol (100 nM) for 24 h and the caspase 3/7 activities were measured by Caspase-Glo 3/7 Assay (Promega). Cell death was also determined by flow cytometry-based Annexin-V/PI staining in SKOV3 cells. **: p<0.01, ***: p<0.001 (unpaired Student’s t-test).
(C-E) MCF7, SKOV3, and OVCAR8 cells were treated with DMSO (control), PKR inhibitor C16 (1 μM), Taxol (100 nM) or the combination. Apoptosis was determined by Western blot analysis using cleaved (cl)-PARP.
(F, G) MCF7, SKOV3, OVCAR8, and TOV21G cells were treated with DMSO (control), PKR inhibitor C16 (1 μM), Taxol (T, 100 nM) or the combination. Apoptosis was determined by Caspase-Glo 3/7 Assay (Promega) and flow cytometry-based Annexin-V/PI staining. **: p<0.01; ***: p<0.001 (unpaired Student’s t-test).
(H) Western blots confirm establishment of PKR-overexpressing cell lines.
(I, J) Enhanced expression of PKR promotes cell death in response to Taxol treatment. TOV21G, SKOV3 or MCF7 (control and PKR-OE) cells were treated with Taxol (100 nM) for 24 h. Apoptosis was determined by the levels of cleaved PARP (I) or caspase3/7 activities (J).
(K) PKR regulates survival in response to Taxol treatment. Clonogenic assays were performed in SKOV3 and MCF7 (control, PKR-KO, PKR-OE) cells. OE: overexpression. Data in panels B, F, G, J, and K are expressed as mean ± SEM from three independent experiments. *: p<0.05, **: p<0.01, ***: p<0.001 (unpaired Student’s t-test).