Fig. 6.

Ibuprofen enhances cisplatin efficacy in mouse model. A) Male BALB/c nude mice (5 weeks of age) were injected with 1 × 10⁶ H1299 cells. When tumor volumes reached approximately 100–200 mm³ (defined as weak 0, W0), cisplatin (5 mg/kg) was intraperitoneally injected one time a week and ibuprofen (25 mg/kg) was orally administrated three times a week. Total three treatment cycles were conducted, which was indicated by red arrows. Tumor volumes were determined once per week. ^★, <0.05; ^★★, <0.01. B) Tumor masses of individual experimental group were shown after sacrifice at W4. C) The representative working model in this study. EFHD2 contributes to intrinsic and acquired resistance of NSCLC to cisplatin through activating the NOX4-ROS-ABCC1 pathway to increase cisplatin efflux. Ibuprofen treatment leads to the proteasomal and lysosomal degradation of EFHD2. NOX4 inhibitor GKT137831 and ROS scavenger NAC were potentially capable of inhibiting ABCC1 in lung cancer. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)