Figure 5.
TRAM-34 can reverse the function of KCNN4. A. The schematic diagram of TRAM-34, a specific inhibitor of KCNN4. B. Cell proliferation assays were conducted to determine the impact of TRAM-34 on cell growth in MDA-231/KCNN4-OE or HS578T/KCNN4-OE cells. C, D. Cytotoxicity assays were performed to examine the influence of TRAM-34 (5 ug/ml) on sensitivity to gemcitabine or Ara-C, in MDA-231/KCNN4-OE or HS578T/KCNN4-OE cells, respectively. E. Western blot analysis of the activity of the KCNN4-RAS-MAPK/PI3K-AKT-BCL2A1 pathways under treatment with an increasing dose of TRAM-34 in HS578T/KCNN4-OE cells. F, G. The responses of mice given a constant dose of gemcitabine with or without TRAM-34 and tumor volumes are presented as indicated (n = 7 for each group). H. Representative IHC images of KCNN4 staining in xenograft tumor samples. I. Quantification of KCNN4 expression in xenograft tumor samples. The P values were two-tailed from matched t tests, with * indicating P < 0.05, *** indicating P < 0.001, and **** indicating P < 0.0001. Experiments were performed in triplicate, and representative results are shown.