Extended Data Fig. 10: The combinatorial regimen of SMART1 and AR12 induces potent tumor suppression in KRAS-mutated CRC.
From: Targeting Smurf1 to block PDK1–Akt signaling in KRAS-mutated colorectal cancer
a–c, Tumor tissues from CRC patients were injected subcutaneously into NOD-SCID mice, and two CRC PDX models (CO-04-0700 and CO-04-0114) were generated. Tumor volume (a) and weight (b) were monitored, and individual tumors (c) were shown (n = 4 mice). d, The heatmap of relative mRNA level of genes involved in PI3K/Akt/mTOR signaling in tumor tissue from these two patients. e, Tumor lysates of PDX models treated with SMART1 were collected for PDK1 neddylation assay and followed by IB analysis. f,g, Individual tumors (left) and tumor weight (right) of PDX models (CO-04-0070 (f) and CO-04-0108 (g)) treated with different combinatorial regimens. h, IB and IP product for PDK1 neddylation and indicated proteins in the tumor tissues from two PDX models. i,j, Body weight measurements showing MLN4924/AR12 or SMART1/AR12 does not affect weight of tumor-bearing mice. Immunoblots are representative of three independent experiments. Error bars denote the mean ± s.e.m. Statistical analyses were performed by unpaired two-tailed Student’s t test.
