Expression data from MDSC treated with STAT3 inhibitor Napabucasin
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ABSTRACT:
PROVIDER: PRJNA781650 | ENA |
REPOSITORIES: ENA
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Project description:MDSC (myeloid-derived suppressor cells) were generated in vitro using IL-6 and GM-CSF. To identify the role of STAT3 in MDSC, we treated the generated cells for 24 hours with DMSO (control) or 1 µM STAT3 inhibitor Napabucasin (also known as BBI608) and compared their expression profile by microarray. We found genes and pathways that are up- or downregulated upon STAT3 inhibition in MDSC.
2022-03-23 | GSE189147 | GEO
Project description:Signal transducer and activator of transcription 3 (STAT3) is a pivotal oncogenic driver in multiple myeloma (MM), where its constitutive activation promotes malignant plasma cell proliferation, survival, and drug resistance in the bone marrow microenvironment. Despite therapeutic advances, MM remains incurable due to persistent STAT3-driven tumorigenesis and the resilience of MM stem cells. Here, we investigated the therapeutic potential of Napabucasin (BBI608), a novel STAT3 inhibitor, in MM. Our data demonstrate that BBI608 potently suppresses MM cell proliferation in vitro and in vivo, while significantly impairing clonogenic potential and inducing robust apoptosis. Mechanistically, BBI608 exhibits dual efficacy by not only targeting bulk tumor cells but also eradicating the stem-like compartment of MM cells, addressing a critical therapeutic challenge. Moreover, we reveal that BBI608 triggers immunogenic cell death (ICD) via activation of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), which subsequently enhances T-cell-mediated anti-tumor immunity. Our findings underscore STAT3 inhibition as a promising strategy to simultaneously eradicate MM cells, target stem cell reservoirs, and harness anti-tumor immunity, providing a robust rationale for clinical translation of BBI608 in MM therapy.
2026-08-12 | GSE299035 | GEO
Project description:KRASG12C inhibitors have demonstrated clinical efficacy in KRASG12C-mutant non-small cell lung cancer (NSCLC), yet adaptive resistance limits their sustained therapeutic benefit. Through high-throughput screening of a pharmacological library, we identified a potent synergistic interaction between the KRASG12C inhibitor sotorasib and the signal transducer and activator of transcription 3 (STAT3) inhibitor napabucasin in KRASG12C-mutant NSCLC models. This combination exhibited superior anti-neoplastic activity compared to monotherapy in vitro and across diverse in vivo models. Mechanistically, KRASG12C inhibitor induced compensatory STAT3 activation, leading to adaptive resistance to sotorasib, which was abrogated by napabucasin. Notably, we elucidated a novel function of STAT3 in regulating HLA-B expression, an inhibitory ligand for natural killer (NK) cells, upon KRASG12C inhibition. The combination therapy enhanced NK cell-mediated cytotoxicity by disrupting the direct binding of phosphorylated STAT3 to the HLA-B promoter to downregulate its expression on neoplastic cells. Our findings unveiled an unexpected immunomodulatory mechanism underlying the synergism between KRAS and STAT3 inhibition, highlighting the potential of concurrently targeting oncogenic signaling cascades and the tumor microenvironment. This study provides a compelling rationale for the clinical evaluation of combined KRASG12C and STAT3 interruption in KRASG12C-mutant NSCLC patients, potentially offering a novel therapeutic strategy to overcome resistance and improve clinical outcomes.
2025-05-07 | GSE272914 | GEO
Project description:Myeloid derived suppressor cells (MDSC) playing the immune suppressive roles in tumor bearing host consists of two major subsets of granulocytic and monocytic cells. Granulocytic MDSC (G-MDSC) express CD11b+ Gr-1high Ly6G+ Ly6Clow and produce high level of reactive oxygen species (ROS). Interestingly, neutrophils are well known ROS producing cells during immune defensive process and share same surface markers with G-MDSC. These similar features always brought the fundamental questions what’s the difference between G-MDSC and neutrophils but it’s not yet proven clearly. In this study, we examined the gene expression of G-MDSC and neutrophils using Affymetrix microarray G-MDSC (CD11b+Ly6G+Ly6Clow) were purifed from splenocytes in EL4 lymphoma tumor bearing mice by positive selection of Ly6G using microbeads isolation. Neutrophils were purified from ascitic fluids induced after injection of milk protein, casein by negative selection of F4/80 and positive selection of Ly6G using microbeads isolation. Their RNA was extracted and gene expression was analyzed using Affymetrix microarray.
2011-03-10 | E-GEOD-24102 | biostudies-arrayexpress
Project description:Activation of Signal Transducer and Activator of Transcription 3 (STAT3) is common in prostate cancers. STAT3 may induce cell proliferation and resistance to apoptosis, as well as promote tumor angiogenesis, invasion, and migration by activating gene expression. Many STAT3-dependent transcriptional responses are mediated through protein-protein interactions that involve the amino-terminal domain (N-domain). In this study, we found that inhibition of the STAT3 N-domain using novel inhibitor ST3-Hel2A-2 induces apoptotic death in prostate cancer cells. The cell death was accomponied by robust activation of pro-apoptotic gene. Using chromatin immunoprecipitation and tiling human promoter arrays (ChIP-chip), we have defined genome-wide targets of STAT3 in DU145 prostate cancer cells. We found that upregulated pro-apoptotic genes were bound by STAT3 in prostate cancer cells, and that STAT3 binding was decreased following inhibition of the STAT3 N-domain. DU145 cells were treated with ST3-Hel2A-2 or DMSO as a control for 3 hr. Total RNA has been extracted and prepared for hybridization on Affymetrix HG-U133A 2.0 arrays.
2010-12-07 | E-GEOD-25866 | biostudies-arrayexpress
Project description:Many patients have cancers that have increased activity of a protein called STAT3 that contributes critically to the development and growth of their cancer. Despite our knowledge of STAT3’s importance to cancer, scientists and doctors have not developed a drug that targets it and that patients can take to treat their cancer more effectively than treatments that are now available. Tvardi Therapeutics, Incorporated has developed a compound, TTI-101, which can be given by mouth and acts as a direct inhibitor of STAT3. Administration of TTI-101 to mice demonstrated that it blocked growth of cancers of the breast, head and neck, lung, and liver and it was safe when administered at high doses to mice, rats, and dogs. In this application, Tvardi is proposing to further develop TTI-101 for treatment of solid tumors for which the prognosis is dismal. The investigators will determine how safe it is when administered to patients with cancer, determine whether an adequate dose can be administered to patients with cancer that will block STAT3 in their cancer, and determine whether treatment with TTI-101 leads to reduced growth of their cancer.
| 2247646 | ecrin-mdr-crc
Project description:To investigate the effect of Napabucasin (BBI608) on liver microenvironment, mice were pretreated with Napabucasin or vehicle control (1% NaCMC) via daily gavage for one week.
2026-07-01 | GSE273353 | GEO
Project description:Myeloid derived suppressor cells (MDSC) playing the immune suppressive roles in tumor bearing host consists of two major subsets of granulocytic and monocytic cells. Granulocytic MDSC (G-MDSC) express CD11b+ Gr-1high Ly6G+ Ly6Clow and produce high level of reactive oxygen species (ROS). Interestingly, neutrophils are well known ROS producing cells during immune defensive process and share same surface markers with G-MDSC. These similar features always brought the fundamental questions what’s the difference between G-MDSC and neutrophils but it’s not yet proven clearly. In this study, we examined the gene expression of G-MDSC and neutrophils using Affymetrix microarray
2011-03-10 | GSE24102 | GEO
Project description:Activation of Signal Transducer and Activator of Transcription 3 (STAT3) is common in prostate cancers. STAT3 may induce cell proliferation and resistance to apoptosis, as well as promote tumor angiogenesis, invasion, and migration by activating gene expression. Many STAT3-dependent transcriptional responses are mediated through protein-protein interactions that involve the amino-terminal domain (N-domain). In this study, we found that inhibition of the STAT3 N-domain using novel inhibitor ST3-Hel2A-2 induces apoptotic death in prostate cancer cells. The cell death was accomponied by robust activation of pro-apoptotic gene. Using chromatin immunoprecipitation and tiling human promoter arrays (ChIP-chip), we have defined genome-wide targets of STAT3 in DU145 prostate cancer cells. We found that upregulated pro-apoptotic genes were bound by STAT3 in prostate cancer cells, and that STAT3 binding was decreased following inhibition of the STAT3 N-domain.
2010-12-07 | GSE25866 | GEO
Project description:Activation of Signal Transducer and Activator of Transcription 3 (STAT3) is common in prostate cancers. STAT3 may induce cell proliferation and resistance to apoptosis, as well as promote tumor angiogenesis, invasion, and migration by activating gene expression. Many STAT3-dependent transcriptional responses are mediated through protein-protein interactions that involve the amino-terminal domain (N-domain). In this study, we found that inhibition of the STAT3 N-domain using novel inhibitor ST3-Hel2A-2 induces apoptotic death in prostate cancer cells. The cell death was accomponied by robust activation of pro-apoptotic gene. Using chromatin immunoprecipitation and tiling human promoter arrays (ChIP-chip), we have defined genome-wide targets of STAT3 in DU145 prostate cancer cells. We found that upregulated pro-apoptotic genes were bound by STAT3 in prostate cancer cells, and that STAT3 binding was decreased following inhibition of the STAT3 N-domain. STAT3 siRNA knockdow confirmed specificity of STAT3 binding and changes in gene expression. DU145 cells were treated with STAT3 siRNA or scrambled siRNA for 48hr. Total RNA has been extracted and prepared for hybridization on Affymetrix HG-U133A 2.0 arrays.
2010-12-07 | E-GEOD-25867 | biostudies-arrayexpress