Figure 4
Inhibition of SR-BI by the small-molecule BLT-1 inhibits proliferation of MDA-MB-231 cells. (A) Pharmacologic inhibition of SR-BI in MDA-MB-231 cells inhibits cellular proliferation. MDA-MB-231 shCTL cells were incubated in the presence of the indicated doses of BLT-1 and 3H-thymidine added to the culture media for 6 hours. At this time, the assay was stopped, and lysates were collected. Columns represent the mean 3H-thymidine incorporation (cpm/μg protein); bars represent ± SD. Results obtained with shSRBI MDA-MB-231 CTL (0 nM BLT-1) are significantly different from those obtained with shCTL 0 nM BLT-1 (CTL) (a, P < 0.001), shCTL 0.1 nM BLT-1 (b, P < 0.001), and shCTL 1.0 nM (c, P <0.05). Results obtained with shCTL MDA-MB-231 CTL (0nM BLT-1) were significantly different from those obtained with shCTL 50 nM BLT-1 (d, P <0.001), shCTL 75 nM BLT-1 (e, P < 0.001), and shCTL 100 nM (f, P < 0.001). Significance was determined by one-way ANOVA with Tukey's post-test analysis. (B) Pharmacologic inhibition of SR-BI attenuates signaling in MDA-MB-231 cells. Western blot analysis was performed with extracts obtained from shSRBI MDA-MB-231 cells treated with vehicle, shCTL MDA-MB-231 cells treated with vehicle, and shCTL MDA-MB-231 cells treated with BLT-1 (50 nM). Cells were serum starved overnight, incubated with vehicle alone or BLT-1 for 3 hours, and then treated with 10% FBS for 30 minutes.