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. 2024 May 28;10:261. doi: 10.1038/s41420-024-02033-z

Fig. 6. TRZ2 acts synergistically with conventional chemotherapeutics and potentiate cytotoxic effects.

Fig. 6

A Effect of TRZ2 combination with chemotherapeutic drugs 5-FU, oxaliplatin (OX), irinotecan (IRI) or with the triplet (FOXIRI), on HT29 cells, as assessed by median-drug effect analysis method. The CompuSyn generated graph shows the combination index (CI) to the growth-inhibitory effect of each drug (FA). Values below the horizontal line (CI = 1) indicate synergism. B Caspase-3/7 activity was determined in HT29 cells treated with TRZ2 alone or in combination (10 µM; 1:1 treatment ratio) for 24 h, using the Caspase-Glo 3/7 assay. C Representative immunoblots of necroptosis mediators RIPK1, RIPK3, MLKL, and respective phosphorylated forms in whole-cell extracts from HT29 cells exposed to indicated drug combinations (10 µM; 1:1 treatment ratio) for 24 h (top left) and quantifications of p-RIPK1/RIPK1 (top right), p-RIPK3/RIPK3 and p-MLKL/MLKL (bottom) ratios. Blots were normalized to endogenous β-actin. DMSO was used as a vehicle control. Results are expressed as mean ± SEM fold-change to control, from at least three independent experiments. #p < 0.05 and §p < 0.001 from control vehicle-treated cells; *p < 0.05 from TRZ2-treated cells.