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. Author manuscript; available in PMC: 2012 Sep 13.
Published in final edited form as: Cancer Cell. 2011 Sep 13;20(3):400–413. doi: 10.1016/j.ccr.2011.08.014

Figure 1. Therapeutic effects of rapamycin and ER stress inducing agents on MPNSTs.

Figure 1

(A) Immunoblots of tumor tissue derived from Nf1/p53 mutant murine MPNSTs and normal peripheral nerve (NN). BIP, phospho-EIF2a (pEIF2α) and the spliced form of XBP-1 (sXBP-1) indicate UPR activation. (B) Immunoblots of pEIF2α and sXBP-1 in MPNST cells after 4 hours of 100nM thapsigargin (TG) or 0.5ug/ml tunicamycin (TN). Actin is a loading control. (C) LD50 values in response to TG or TN (48 hours) in normal cells (IMR90), human MPNST cell lines (S462, SNF96.2) and mouse MPNST cell lines (185-3, 1A50). (D) Growth curves comparing the effects of different doses of thapsigargin and tunicamycin in S462 human MPNSTs and IMR90s. (E) Waterfall plot depicting tumor growth after 10 days of treatment with vehicle (blue), thapsigargin (red), rapamycin (yellow) and rapamycin/thapsigargin (green). The left y-axis indicates the log2 of tumor fold growth vs. day 0 and the right y-axis shows the change in fold volume. The table shown reports mean and standard deviation for each treatment arm (n=8) and mean tumor shrinkage. (F) Graph depicting the change in tumor size over time. Three animals on the rapamycin/thapsigargin combination are shown (green). For simplicity the yellow line is an average volume of rapamycin treated tumors (n=8). Blue and red lines represent vehicle and thapsigargin treated animals respectively. (G) H&E stained tumor remnants from animals treated with rapamycin/thapsigargin. Sections from tumors after (a) 107 days of treatment, (b) 35 days (c), 21 days (d) 4 days, showing pyknotic nuclei throughout the tumor. All images were taken using 10× objective, except (d) which has been magnified to 40×. (See also Figure S1)