Figure 2
From: The novel drug candidate S2/IAPinh improves survival in models of pancreatic and ovarian cancer
Chemical linkage to sigma-2 ligand SW43 leads to the functionally enhanced drug conjugate S2/IAPinh with increased activity over IAPinh alone. (A) Human pancreatic cancer cell lines AsPC-1, HPAC, and MiaPaCa-2, mouse pancreatic cancer cell lines KP2, and human ovarian cancer cell lines OVCAR3 and OVCAR 8 were treated with different concentrations (0, 3.125, 6.25, 12.5, 25, 50, and 100 µM) of SW43 alone, IAPinh alone, an equimolar mix (SW43 + IAPinh) and S2/IAPinh alone for 24 h and cell viability was determined by CellTiter-Glo Luminescent Viability Assay (Promega). Two-way ANOVA; NS = not significant. (B) Representative images of TUNEL labeled apoptosis cells in HPAC cells treated with vehicle, SW43 (6 µM), IAPinh (6 µM), or S2/IAPinh (6 µM) for 6 h. Nuclei were stained in blue with Hoechst, TUNEL positive cells are in red. Scale bars are equal to 50 µm. (C) Quantification of TUNEL positive cells per area in each treatment group. Data are shown as means ± SEM; **P < 0.01. (D) Organoid cultures from patients with pancreatic cancer (hF3, hF23, hF44, hM1E, hM19A) were treated with escalating concentrations of S2/IAPinh (0, 0.01, 0.02, 0.05, 0.12, 0.28, 0.66, 1.52, 3.6, 8.2, 18.76, 43.2, and 100 µM) for 5 days and cell viability was determined by CellTiter-Glo Luminescent Viability Assay (Promega) (n = 4 per cell line).
