TREX1 depletion resensitizes resistant SCLC tumors to chemotherapy. A, Schematic of the method used to establish cisplatin-resistant H82 (H82-CispR) cells. B, Expression levels of TREX1 in H82 and H82-CispR (Scr and sgTREX1) cells were compared by immunoblotting. C, Expression levels of IFNB and IFIT1 genes were compared between Scr and sgTREX1 H82-CispR cells by qPCR (mean ± SEM; n = 3). D, Growth curves of the indicated cells treated with DMSO (Left) or 1.0-µmol/L cisplatin (Right) were compared (mean ± SEM; n = 3). E, Tumor growth curves of Scr and sgTREX1 H82-CispR tumors (n = 5), treated with 5-mg/kg cisplatin, were compared. F, Tumor growth curves of Scr and sgTREX1 H69AR tumors (n = 6), treated with 5-mg/kg cisplatin, were compared. G, Expression levels of the IFNB gene were compared between shCtrl and shTREX1 H1048 cells treated w/wo DOX (mean ± SEM; n = 3). H, Tumor growth curves of shCtrl and shTREX1 H1048 tumors (n = 6), treated with 5-mg/kg cisplatin, were compared. I, Schematic model of antitumor effects caused by TREX1 depletion. Data represent mean ± SEM. ns, not significant; *, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001 by unpaired Student t test (C, E, and F) and one-way ANOVA followed by Dunnett’s multiple comparison test (D), and two-way ANOVA followed by Tukey’s multiple comparison test (G and H). (I, Created with BioRender.com.)
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Murayama et al. (2024) studied this question.
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