Low-to-moderate HMGA2 expression increases irinotecan chemosensitivity of PDX models.

(A) Western blot using anti-HMGA2 antibody Ab41878 exhibiting high HMGA2 detection sensitivity (top panel). HMGA2 expression from representative propagated tumors (indicated by the corresponding mouse number) from each PDX model before inoculation into the treatment groups (two independently propagated samples are shown for model no 1030). We compared their HMGA2 expression levels with two cancer cell lines as standards for SN38 sensitivity: H1299 cells, which exhibit a degree of SN38 resistance due to high HMGA2 levels, and HT1080 C1 cells, which exhibit SN38 sensitivity due to low/moderate HMGA2 levels. The complete set of propagated tumors for each PDX model chosen for treatment is shown in S6 Fig and indicated as mouse no. Quantification (bottom panel) of HMGA2 expression relative to H1299 (set as 1) using ImageJ software (n = 3 independent experiments). Error bars show SD. Unpaired two-tailed t-tests. * p (B) Tumor growth kinetics (Day 0 to Day 39) of five PDX models (n = 6 animals/model) in Irinotecan treatment group. Dotted lines indicate mean starting volume of all PDX models. Two-way ANOVA followed by Tukey’s multiple comparisons. Error bars show SEM. * p (C) Tumor growth kinetics (Day 0 to Day 39) of five PDX models (n = 6 animals/model) in vehicle group. Two-way ANOVA followed by Tukey’s multiple comparisons. Error bars show SEM. ns not significant. (D) Tumor growth inhibition (TGI) of each PDX model at day 39 (Plotted as percentage). TGI is calculated taking the physiological growth of the tumor (vehicle group) into account. Dotted lines indicate 100% TGI level. Two-way ANOVA followed by Tukey’s multiple comparisons. Error bars show SEM. * p (E) Graphical representation of the correlation between HMGA2 expression and tumor outcomes due to irinotecan treatment in colorectal PDX models used in the study.