Fig. 6: ZIP1⁺ fibroblasts promote chemoresistance of lung cancer cells in vitro and in vivo.

a Experimental design (left) and results of DNA damage (γ-H2AX expression) in LLC-GFP-luc cells co-cultured with Zip1^+/+ or Zip1^−/− MEFs with DOX (3 μM) treatment. Mean ± SEM, n = 4. Two-tailed t-test. b DOX accumulation in LLC-GFP-luc tumour cells co-cultured with Zip1^+/+ or Zip1^−/− MEFs with DOX (3 μM) treatment. Mean ± SEM, n = 4. Two-tailed t-test. c ABCB1 expression in LLC-GFP-luc tumour cells co-cultured with Zip1^+/+ or Zip1^−/− MEFs for 24 h. Mean ± SEM. Ctl, Zip1^+/+: n = 3; Zip1^−/−: n = 6. Two-tailed t-test. d DOX accumulation in LLC-GFP-luc tumour cells 6 h after DOX injection in tumour-bearing Zip1^+/+, Zip1^+/− and Zip1^−/− mice. DOX (10 mg/kg) was intravenously injected into the mice at day 10 post-transplantation. Mean ± SEM. Zip1^+/+: n = 4; Zip1^+/−, Zip1^−/−: n = 5. One-tailed Kruskal–Wallis test. e ABCB1 expression in LLC-GFP-luc cells transplanted into Zip1^+/+ and Zip1^−/− mice at day 10 post-transplantation. Mean ± SEM, n = 5. Two-tailed t-test. f Tumour growth curves for Zip1^+/+ and Zip1^−/− mice treated with DOX or PBS. Arrows, DOX injection. Mean ± SEM. P values are for indicated time points. Zip1^+/+ PBS (n = 11), Zip1^−/− PBS (n = 12), Zip1^+/+ DOX (n = 8), Zip1^−/− MEFs DOX (n = 10). g Tumour growth curves for co-injection of Zip1^+/+ or Zip1^−/− MEFs with LLC-GFP-luc cells, with DOX or PBS treatment. Arrows indicate DOX injection. Zip1^+/+, Zip1^−/− MEFs PBS, Zip1^−/− MEFs DOX: n = 9; Zip1^+/+ MEFs DOX: n = 6. Mean ± SEM. h Tumour growth curves for mice inoculated with LLC cells and mCAFs with a tet-off system-controlled expression of Zip1 (TET-Zip1). Mice were administered PTX, with or without doxycycline (Dc) treatment. Mean ± SEM. Arrow, PTX (10 mg/kg) treatment. TET-mock, TET-Zip1 PBS: n = 6; TET-Zip1 PTX, TET-Zip1 PTX + Dc: n = 5. Two-way ANOVA test for tumour growth curve comparison. Source data are provided as a Source Data file (a–h).