Fig. 6: Inhibitors of BACE, ADAM, and MMP lower MSLN shedding.
From: Multiple proteases are involved in mesothelin shedding by cancer cells
a Twenty micromolar of LY2886721 or Lanabecestat were incubated with KB31, MS751, T3M4, AsPC1, or KLM1 cells in 96-well plates for 48 h. MSLN in culture media was measured (KB31, both P < 0.0001; KLM1, P = 0.77 and 0.38; T3M4, P = 0.0006 and 0.031; OVCAR8, P = 0.118 and 0.987; MS751, P < 0.0001 and 0.009; AsPC1, both P < 0.0001, n = 3). b In all, 10 µM TMI-1 or 10 µM Marimastat were incubated with cells and shed MSLN measured (TMI-1, P = 0.084, <0.0001, 0.002, 0.00014; Marimastat: P = 0.0002, 0.0003, <0.0001, <0.0001, n = 3). c–f KB31 cells (c, d) were treated with 10 µM Lanabecestat or 10 µM Marimastat or both, OVCAR8 (e, f) were treated with TMI-1 or Marimastat or both. Shed MSLN level are shown (c P = 0.0005, <0.0001, <0.0001; e P = 0.002, 0.0023, 0.0027, n = 3). KB31 (d) or OVCAR8 (f) were incubated with inhibitors for 20 h, then SS1P at indicated concentration was added for 72 h. Cell viability was measured by WST-8 assay. Lana Lanabecestat, Mari Marimastat (ns not significant, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001).
