Fig. 8
SLC25A1-dependent mitochondrial respiration drives therapy resistance. a, b T1 and T2 cells were treated with cisplatin (0.5–1 μM) or AZD9291 (1 μM), as indicated in each panel, passaged in the presence of the drugs several times, then subjected to OCR analysis with the Seahorse analyzer. c SLC25A1 protein levels in T1 and T2 cells cultured in the presence or absence of cisplatin. d FACS analysis of CD166 and CD133 markers in the cisplatin or AZD9291-resistant T1 or T2 cells. e–g T1 e, T2 f and T4 g cells were untreated or treated with the indicated drugs. The concentration of drugs employed is indicated at the bottom of each panel. Viability was assessed with Crystal Violet after 5 days of treatment. Relative (R) index calculations were used to assess the type of drug interactions and are indicated in each panel. The R index is calculated as the expected cell survival (Sexp; the product of relative survival in cisplatin and relative survival in CTPI-2) divided by the observed relative survival in the presence of both drugs (Sobs). Sexp/Sobs = 1.0 denotes an additive interaction, whereas >1.0 denotes a synergistic interaction, R index values approaching 2.0 are indicative of strong synergy. h Kaplan–Meier survival curves relative to SLC25A1 expression in lung AdenoCa patients that received chemotherapy. Red and black lines indicate high and low SLC25A1 expression, respectively. Analysis was performed by using the Km plotter database (http://kmplot.com/analysis/). Bars represent the standard deviation, asterisks refer to **P ≤ 0.01; ***P ≤ 0.001; ****P ≤ 0.0001 by unpaired T-test
