Fig. 6: Targeting O-GlcNAcylation of RRM1 heightens the sensitivity of pancreatic cells to gemcitabine-induced cell death.

A, B Parental and RRM1-T734A PANC-1 cells were treated with indicated concentrations of gemcitabine for three days and subjected to viability analysis. A Cell viability in the absence of gemcitabine treatment was normalized to parental cell numbers (n = 5). ****p < 0.0001 (two-tailed Student’s t-test). B Cell viability following gemcitabine treatment in parental and RRM1-T734A PANC-1 cells was normalized to their respective untreated conditions. C–H Parental PANC-1 (C, D), MiaPaCa-2 (E, F), and BxPC-3 (G, H) cells were exposed to OSMI1 alone or in combination with gemcitabine, then evaluated for viability. C, E, G) show cell viability without gemcitabine treatment, normalized to their corresponding OSMI1-untreated conditions. PANC-1 cells (n = 4); MiaPaCa-2 and BxPC-3 cells (n = 8). **p < 0.01; ***p < 0.001; ****p < 0.0001 (two-tailed Student’s t-test). D, F, H Cells were pre-exposed to OSMI1 for a day and then subjected to combined treatment with indicated concentrations of gemcitabine for three days to assess cell viability. B, D, F, H All IC₅₀ were determined by GraphPad Prism 9. Analysis model: asymmetric sigmoidal, 5PL, X is log (concentration). I Proposed model illustrating how O-GlcNAcylation of RRM1 impacts pancreatic cancer malignancy.