Fig. 4: Targeting LOX or downstream FAK/Src overcomes TNBC chemoresistance in vivo.

a Tumor growth in MDA-MB-231 xenografts treated with doxorubicin until resistance develops followed by treatment with the combination of doxorubicin (2.5 mg/kg) and the LOX inhibitor, BAPN (100 mg/kg) (n = 12, 7, and 8 tumors for vehicle, Doxo and Doxo+BAPN, respectively). b Tumor growth rates relative to vehicle from a. c Cumulative survival of mice from a. Mice were sacrificed when the tumor size cut-off was reached or when the body weight dropped to 80% of the initial body weight (n = 6, 4, and 4 mice for vehicle, Doxo and Doxo + BAPN, respectively). d Percentage change in the body weight of the mice from c. e Relative LOX activity in tumors from a (n = 3). f Representative images of Picrosirius red staining (f) and its quantification (g), in tumors from a (n = 6). h In vivo collagen assay in tumors from a (n = 2 (vehicle), n = 4 (Doxo, Doxo+BAPN)). i Tumor growth in 4T1 syngeneic model upon treatment with doxorubicin and BAPN, alone or in combination (n = 4 mice). j LOX activity in tumors from i (n = 6). k, l Representative images of Picrosirius red staining (k) and its quantification (l) in mice from i (n = 7). m, n Intratumoral doxorubicin levels upon treatment with the combination of doxorubicin and BAPN (n = 6). o Western blot analysis of FAK/Src signaling in combination-treated tumors from i. p, q Change in tumor growth (p) and representative images of tumors (q) in 4T1 model upon treatment with doxorubicin and Saracatinib, alone or in combination (n = 4). r, s Change in tumor growth (r) and representative images of tumors (s) in 4T1 model upon treatment with doxorubicin and PF-562271, alone or in combination (n = 4). Data represents mean ± SD. Two-sided Student’s t-test was used to calculate statistical difference between two groups. Two-way ANOVA test was performed for comparing tumor growth over time among different treatment groups in i, p, and r. n.s. not significant. Scale bar = 400 µm for f, k; 200 µm for m, and 1 cm for q, s. Source data are provided as a Source data file.