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. 2015 May 27;6(30):29833–29846. doi: 10.18632/oncotarget.4006

Figure 4. SIM-mediated inhibition of Ras/ERK1–2 and RhoA/RhoA kinase signaling pathways.

Figure 4

IGHV UM cells, cultured alone or in the presence of the murine stromal cell line M2–10B4, were exposed to 1 μM SIM. A. Cholesterol and FPP production. The amount of cholesterol and FPP produced by IGHV UM cells was significantly increased after 24-hour co-culture with SCs (p = 0.007 and p = 0.009, respectively). SIM significantly reduced the levels of cholesterol and FPP in IGHV UM cells both in the absence (p = 0.04 and p = 0.05, respectively) and in the presence (p = 0.03 and p = 0.01, respectively) of M2–10B4 SCs. B. Ras and ERK1–2 kinase activity. Co-culture with M2–10B4 SCs increased the levels of Ras-GTP and phospho-ERK1–2 kinase. SIM reduced the expression of the active forms of Ras and phospho-ERK1–2 kinase in IGHV UM cells, both in the absence and in the presence of SCs. Results are from two representative experiments (UPN, unique patient number). C. RhoA and RhoA kinase activity. Twenty four-hour co-culture with M2–10B4 SCs significantly increased the levels of expression of RhoA GTP and RhoA Kinase (p = 0.0005 and p = 0.0024, respectively). The expression of RhoA-GTP and RhoA kinase was significantly reduced by SIM, both in the absence (p < 0.0001 and p < 0.0001, respectively) and in the presence (p < 0.0001 and p < 0.0001, respectively) of SCs. In panels A and C results are from 8 side-by-side experiments. Box and whiskers plots represent median values, first and third quartiles, and minimum and maximum values for each dataset.