Fig. 8

SETDB1 inhibitor TTD-IN with LINC00115 ASO sensitizes PTX-resistant cell response to chemotherapy. A Effects of treatment of SETDB1 inhibitor TTD-IN (25 µM) or/and LINC00115 ASO (L115-ASO, 1 µM) on expression of HIF1α, SOX2, and CD44 in MDA-MB-231/PTX_R and BT549/PTX_R cells. Cells were treated with TTD-IN or L115-ASO as indicated. B, C Cell proliferation (B) and invasion (C) analyses in MDA-MB-231/PTX_R and BT549/PTX_R cells. D, E Effects of treatment of SETDB1 inhibitor TTD-IN (25 µM) or/and L115-ASO on lung metastasis (D) and animal survival (E). F Treatment schedules for the administration of PTX (10 mg/kg, intraperitoneal injection once daily), TTD-IN (50 mg/kg, intraperitoneal injection once daily), or/and L115-ASO (10 mg/kg, intraperitoneal injection once daily) to mice grafted with MDA-MB-231/PTX_R cells (n = 6). Control mice received a placebo (vehicle). i.v., intravenous injection. i.p., intraperitoneal injection. G Representative bioluminescence images in (F) on day 21. H Quantification of the bioluminescence activity of MDA-MB-231 tumor xenografts in (F). I Quantification of the number of surface lung metastasis in panel (F). J Kaplan-Meier survival analysis of mice with MDA-MB-231 tumor xenografts (n = 6). ns, no significance. Data are representative of two or three independent experiments with similar results. Error bars, ± SEM. **P < 0.01, ***P < 0.001, by paired two-way Student’s-test, one-way ANOVA, or log-rank analysis