FIGURE 1.

Highly brain metastatic lung cancer cells showed significant resistance to platinum‐based chemotherapeutic agents. (A) Schematic illustration of the in vivo isolation of metastatic populations (BrM1, BrM2, and BrM3) from the PC9 lung adenocarcinoma line and the subsequent metabolomics and proteomics analyses. (B, D) PC9 and PC9‐BrM3 cells were treated with different doses of cisplatin (B) or carboplatin (D) for 72 hours and CCK‐8 assays were performed to determine their viability (n = 3, **P < 0.01). (C, E) Survival of PC9 and PC9‐BrM3 cells after treatment with certain concentrations of cisplatin (0, 4, 12 μM) (C) or carboplatin (0, 20, 60 μM). (E) Results of clonogenic assays showing the treatment effect. Pixel density quantification of clonogenic assays is shown as histogram (n = 3, *P < 0.05). (F‐H) Nude mice were injected subcutaneously with the indicated PC9 or PC9‐BrM3 cells (5×10⁶ cells/mouse) and treated with cisplatin (5 mg/kg/i.p., once every 5 days) or with DMSO as control (Ctrl) (n = 5 mice/group). Tumor size was measured every 3 days using caliper to plot the growth curve. (E) The tumor mass was weighed at the end of the experiment (F and G). (*P < 0.05, ****P < 0.0001)