Fig. 7: Targeting STING and ER homeostasis enhances the efficacy of chemotherapy.
From: IRE1α translational suppression potentiates STING-dependent chemoresistance in pancreatic cancer
a Schematic of cancer model: Sting-/- Panc02 cell -transplanted mice received four intraperitoneal injections of Chemo drugs (Cis, 3 mg kg−1; 5FU, 25 mg kg−1; Irinotecan, 25 mg kg−1) and four peritumoral TM injections (TM, 0.3 mg kg−1). Tumors from immunodeficient (b, c) or immunocompetent (d, e) mice at the end of experiment (Day 16 and Day 19, respectively). Tumors weight quantification in immunodeficient mice (b, n = 7 mice per group), and in immunocompetent mice (d, n = 6 mice per group), representative of two independent repeats. f Proposed model illustrating the synchronized effect of STING pathway inhibition and ER stress induction, in conjunction with chemotherapy. STING is negatively regulated by IRE1α in PDAC, while chemotherapy-induced downregulation of IRE1α amplifies STING signaling and promotes cancer cell survival. However, this dysregulated proteostasis network increases susceptibility to ER stress-inducing agents. All values are presented as mean ± SEM. Statistical significance was determined using an unpaired, two-tailed Student’s t-test (b, d). *, p < 0.05; **, p < 0.01; ***, p < 0.001; ****p < 0.0001.
