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. 2024 Feb 16;27(3):109247. doi: 10.1016/j.isci.2024.109247

Figure 6.

Figure 6

Chemoresistance in fetal/regenerative/revival cells can be overcome by inhibiting TEAD/TNF

(A) Cell proliferation assay after 72 h treatment with 5-Fluorouracil (5-FU) in seven 3D MG and 2D HC cultures are shown (left panel). The median inhibitory concentration (IC50) of 5-FU is shown (right panel). Data are represented as mean ± SD. Statistical significance: ∗p < 0.05, paired t-test.

(B) Cell proliferation assay after 72 h treatment with Oxaliplatin in seven 3D MG and 2D HC cultures is shown (left panel). IC50 of Oxaliplatin is shown (right panel). Data are represented as mean ± SD. Statistical significance: ∗p < 0.05, paired t-test.

(C) Cell proliferation assay after 72 h treatment with CPT-11 in seven 3D MG and 2D HC cultures are shown (left panel). IC50 of CPT-11 is shown (right panel). Data are represented as mean ± SD. Statistical significance: ∗p < 0.05, paired t-test.

(D) Cell proliferation assay after 72 h treatment with the TEAD inhibitor in seven 3D MG and 2D HC cultures is shown (left panel). IC50 of the TEAD inhibitor is shown (middle panel). Cell viability after 72 h treatment with 5-FU at 20 and 40 μM, TEAD inhibitor at 10 μM and a combination of 5-FU at 20 μM plus TEAD inhibitor at 10 μM is shown (right panel). Data are represented as mean ± SD. Statistical significance: ∗p < 0.05, paired t-test.

(E) Cell proliferation assay after 72 h treatment with the TNF inhibitor in seven 3D MG and 2D HC cultures is shown (left panel). IC50 of the TNF inhibitor is shown (middle panel). Cell viability after 72 h treatment with 5-FU at 20 and 40 μM, TNF inhibitor at 7.5 μM and a combination of 5-FU at 20 μM plus TNF inhibitor at 7.5 μM is shown (right panel). Data are represented as mean ± SD. Statistical significance: ∗p < 0.05, paired t-test.

(F) Representative cell-cycle profiling of control and 5-FU treated 3D MG (upper panel) and 2D HC (lower panel) determined by fluorescence image cytometer NucleoCounter NC-250 system is shown. Cell populations in S and G2/M phases are indicated by a square. The >4N cell populations are indicated by a dashed square.

(G) Representative images of cleaved caspase3 staining (red) of 2D HC after 72 h treatment of DMSO (control) (upper panel) or 5-FU at 40 μM (lower panel) are shown. Images are counterstained with DAPI (blue). The adjacent panels present merged images with Phalloidin (gray) for both control and 5-FU. Scale bars, 50 μm.

(H) Structural changes in actin filaments induced by TNF inhibitor administration are depicted by phalloidin staining. Representative images of phalloidin staining (gray) of 2D HC after 72 h treatment of DMSO (control) (upper panel) or TNF inhibitor at 10μΜ are shown. In the adjacent panels, merged images with DAPI (blue) are presented for control and TNF inhibitor. Scale bars, 50 μm. See also Figure S4 and Videos S6 and S7.