Fig. 6: Phosphorylation of GCLM at T17 contributes to CRC chemoresistance in vivo.
Representative images (a, the black arrowheads indicate the tumor), tumor numbers and average sizes (b) of spontaneous tumors in Gclmfl/fl and GclmiKO mice treated with PBS or oxaliplatin (5 mg/kg). Representative images of H&E, IHC of GCLM, Ki67 and Tunel staining (c), and quantification of Tunel staining (d) of the spontaneous mouse CRC model. The blue arrowheads indicate the adenomas and the red arrowheads indicate the positive cells of Tunel staining. Scale bar = 1 mm (low power image) and 50 μm (high power images). Statistical analysis of the CDX tumor volume and weight after the implantation of endogenous GCLM-knockdown HCT116 (e) and DLD1 (f) cells (2 × 106), which overexpressed rGCLM WT or T17A, T17E mutants, followed by intraperitoneal injections of PBS or oxaliplatin (5 mg/kg). Statistical analysis of the tumor volumes and weights in the PDX #1 (g) and PDX #2 (h) models, followed by intraperitoneal injections of control or P38 inhibitor (P38i, SB203580, 5 mg/kg) and FOLFOX (oxaliplatin 5 mg/kg, 5-fluorouracil 25 mg/kg). n = 6 mice in (b, d, g, h) and n = 5 mice in (e, f). All the data are presented as the mean ± S.D. The P values were calculated by one-way ANOVA (b, d and g, h right) and two-way ANOVA (e–h left).
