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. Author manuscript; available in PMC: 2018 Nov 13.
Published in final edited form as: Cancer Cell. 2017 Oct 19;32(5):624–638.e5. doi: 10.1016/j.ccell.2017.09.013

Figure 5. IMPDH inhibition induces replication stress, DNA damage, and apoptosis in TSC tumors, in an mTORC1-dependent manner.

Figure 5

(A–G) Mice bearing ELT3 xenograft tumors were treated for 5 days with vehicle (Veh), mizoribine (Miz; 150 mg/kg/day), rapamycin (Rap; 1 mg/kg day 1, 3, 5), or mizoribine plus rapamycin. Blood plasma and tumors were collected 3 hr after the final treatment injection. n=3 mice/group

(A–E) Levels of mizoribine in blood plasma (A) or tumors (B), guanylate nucleotides in tumors (C), and AICAR in blood plasma (D) or tumors (E) were measured by LC-MS/MS and presented as mean ± SEM (n=3 mice/group). Data in C-E are graphed relative to vehicle-treated mice. *p<0.05, **p<0.005 by two-tailed Student’s t test.

(F,G) Analysis of indicated proteins by immunoblots (F) and IHC staining on non-necrotic regions (G) from tumors. Scale bar = 0.2 mm.

See also Figure S5.