Fig. 8

Combination of pharmacological and genetic approaches preserving C/EBP-β LIP restores doxorubicin efficacy in resistant xenografts. JC cells, stably transfected with an inducible expression vector for C/EBP-β LIP (JC TetON LIP) were orthotopically implanted into 6 week-old female balb/C mice. When indicated, animals received 1 mg/ml doxycycline in the drinking water (+ doxy) to induce the intratumor LIP expression. Mice were randomized into 4 groups (n = 10 animals/group) and treated once a week for 3 consecutive weeks (days 1, 6, 12 after randomization) as follows: 1) control (ctrl) group, treated with 0.1 ml saline solution intraperitoneally (i.p.); 2) doxorubicin (D) group, treated with 5 mg/kg doxorubicin i.p.; 3) chloroquine+bortezomib (CQ + B) group, treated with 10 mg/kg CQ per os and 0.25 mg/kg bortezomib i.p.; 4) chloroquine+bortezomib+doxorubicin (CQ + B + D) group, treated with chloroquine+bortezomib, followed by doxorubicin after 24 h. a. Tumor growth was monitored daily by caliper measurement. Data are presented as means±SD. *p < 0.001: all treatments vs “-doxy, ctrl” group; °p < 0.05: “+ doxy” treatments vs corresponding “- doxy” treatments; ^#p < 0.001: “+ dox” treatments vs corresponding “- dox” treatments (days 9–18). b. Photographs of representative tumors of each group. c. Sections of tumors from each group of animals were stained with hematoxylin and eosin (HE) or with the indicated antibodies. Nuclei were counter-stained with hematoxylin (10× ocular lens, 20× or 63× objective). Bar = 10 μm