Additional file 1 of Irbesartan overcomes gemcitabine resistance in pancreatic cancer by suppressing stemness and iron metabolism via inhibition of the Hippo/YAP1/c-Jun axis
Creators: name: Zhou, Tianxing
name: Xie, Yongjie
name: Hou, Xupeng
name: Bai, Weiwei
name: Li, Xueyang
name: Liu, Ziyun
name: Man, Quan
name: Sun, Jingyan
name: Fu, Danqi
name: Yan, Jingrui
name: Zhang, Zhaoyu
name: Wang, Yifei
name: Wang, Hongwei
name: Jiang, Wenna
name: Gao, Song
name: Zhao, Tiansuo
name: Chang, Antao
name: Wang, Xiuchao
name: Sun, Hongxia
name: Zhang, Xiufeng
name: Yang, Shengyu
name: Huang, Chongbiao
name: Hao, Jihui
name: Liu, Jing
Publisher: name: figshare
Year: 2024
Subjects: subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Molecular Biology
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Biological Sciences not elsewhere classified
subject: Information Systems not elsewhere classified
subject: Cancer
subject: Hematology
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Virology

description: Additional file 1: Figure S1. Related to Fig. 1. The effects of combination of GEM and the candidates’ drugs (irbesartan, Dapansutrile, Pemigatinib and Dauricine) on GEM-resistant PDO1# (A-D), PDO2# (E-H) and PDO7# (I-L) lines by CelltiterGlo-3D assays. Paired Student’s t-test were used for in vitro experiments. Figure S2. Related to Fig. 2. (A-B) The relative area of organoids per group in Fig. 2C, F were measured by Image J software. (C-D) The fluorescence intensity of Caspase3/7 of organoids per group in Fig. 2C, F were determined by software Image J. (E-F) The mean intensity of Ki67 of organoids per group. (G) Mice body weight per group in Fig. 2I-K were monitored. All experiments were repeated three times independently. Paired Student’s t-test were used for in vitro experiments. Repeated measure two-way ANOVA (time x mice body weight) and post-hoc analyses were used for test mouse body weight between groups. Figure S3. The effects of irbesartan were validated in another 9 patient-derived organoids (PDOs) subcutaneous tumor models in vivo and the tumor growth curves were plotted. Repeated measure two-way ANOVA (time × tumor volume) and post-hoc analysis were used for test tumor growth between groups. Figure S4. The effects of irbesartan were validated in 10 patient-derived xenografts (PDXs) subcutaneous tumor models in vivo and the tumor growth curves were plotted. Repeated measure two-way ANOVA (time × tumor volume) and post-hoc analysis were used for test tumor growth between groups. Figure S5. Irbesartan could significantly reverse GEM resistance in GEM-resistant BxPC-3 cell lines. Figure S6. The expression pattern of c-Jun and its clinical significance in PDAC. Figure S7. The effects of irbesartan on inhibiting c-Jun expression were validated in 10 patient-derived organoids (PDOs) tumors from Fig.2K and Fig. S3 via western blot and q-PCR. Figure S8. The effects of irbesartan on inhibiting c-Jun expression were validated in 10 patient-derived xenografts (PDXs) subcutaneous tumors from Fig.S5, another GEM-resistant BxPC-3 orthotopic tumors from Fig. S6 via western blot and q-PCR. Figure S9. Related to Fig. 4. Figure S10. Related to Fig. 6. Figure S11. Tumoral c-Jun induces chemotherapy resistance of GEM in 2D PDAC models in vitro. Figure S12. Tumoral c-Jun is positively correlated with stemness profiles in PDAC. Figure S13. Data related to Fig. 7. Figure S14. Tumoral c-Jun positively regulates the expression of stemness genes (SOX9/SOX2/OCT4) and iron metabolism genes (FTH1/FTL/TFRC) in PDAC. Figure S15. Data related to Fig. 10. Supplementary table 2. Detailed information of patients whose specimens were used for establishment of PDO models and in vivo PDX mouse models. Supplementary table 5. Correlation of c-Jun expression to clinicopathological features in PDAC. Supplementary table 6. Univariate and multivariate Cox proportional hazards analysis of clinicopathological factors for median overall survival and relapse free survival. Supplementary table 10. detailed information of shRNA oligos sequences for stable knockdown cells (the following oligos sequences were shown as: overhang-target-loop-antisense). Supplementary table 11. detailed information of antibodies used in this study. Supplementary table 12. detailed information of primers used for RT-PCR and Ch-IP in this study. Supplementary table 13. detailed information of sequences of the plasmids used for luciferase analysis (The following DNA sequences were cloned into pGL3.0-basic plasmid).