Fig. 2: Serine promotes carboplatin resistance in NSCLC.

A The serine levels were measured in human LUAD and LUSC tissues. B The serine levels were measured in cell lines derived from human bronchial, LUAD and LUSC. C PC9 or NCI-H1975 cells, cultured in media added with or without serine (1 μM), were treated with carboplatin (100 μM) for 48 h, followed by CCK-8 assay for cell viability. (D-E) NCI-H520 or NCI-H1703 cells, cultured in media with or without serine (-S) or without both serine and glycine (-SG), were treated with or without carboplatin (100 μM) for 48 h, followed by CCK-8 assay. F–H Mice were subcutaneously injected with NCI-H520 cells, fed a control diet (23.3 g/kg glycine and 3.5 g/kg serine) or an equivalent diet supplemented with high serine (high S diet, 20 g/kg serine), serine free (-S diet), or both serine and glycine free (-SG diet), were treated with vehicle (DMSO) or carboplatin (5 mg/kg). Representative images of dissected xenografts from the indicated groups at the end of the experiments are shown in (F). Tumor volume, tumor weight (G) and intratumoural serine levels (H) of subcutaneous xenografts were measured. NCI-H520 cells, grown with or without serine (-S) or without both serine and glycine (-SG), were treated with carboplatin (100 μM) for 48 h, followed by immunoblot analysis for γH2AX expression (I), or FACS assay for ROS level (J). K NCI-H520 cells, grown in control (Ctrl), serine deficient (-S), serine and glycine deficient (-SG), -SG + formate (5 μM), -SG + NAC (1 mM) or -SG + formate + NAC media, were treated with or without carboplatin (100 μM) for 48 h, followed by CCK-8 assay. HCC95 cells, grown with or without both serine and glycine (-SG), or combined with or without NCT-503 (5 μM), were treated with or without carboplatin (100 μM), for 48 h, followed by CCK-8 assay (L) and measurement for cellular serine level (M). *p < 0.05; **p < 0.01; NS not significant.