Excel · study · 2026
Chemotherapy-induced senescent fibroblasts promote NF-kB-mediated tumor aggressiveness, suppressed by Rofecoxib in gastric cancers
Listed in NCBI GEO
Purpose: Chemotherapies for patients with gastric cancers (GCs) has been shown disappointing results in the clinics.
Description
The cancer-associated fibroblasts (CAFs) could be considered one cause of the resistance to chemotherapy in GCs. However, the chemotherapy-induced reprogramming of CAFs and its effects on GC progression and chemotherapy resistance have not been elucidated.
Methods
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IncuCyte and transcriptome were used to identify chemotherapy-induced senescence of CAFs. Screening for drugs to inhibit the senescence of CAFs was performed. The cell proliferation and migration assays and phospho-protein array were performed to investigate the effects of senescent CAFs on GC cells.
Inhibitory effects of screened drugs on CAFs were also evaluated in experimental models. Senescent CAFs and their clinical meanings were also investigated in the human GC tissues undergoing preoperative chemotherapies. Results: Chemotherapy could alleviate proliferation and widen cytoplasm of CAFs.
Some secretory molecules like TNF-α were upregulated in the CAFs with chemotherapy. Chemotherapy-treated CAFs increased the resistance to chemotherapy and the migratory potentials of GC cells. The COX2 inhibitor, one of the screened drugs, has inhibitory effect on chemotherapy-induced senescence CAFs.
Consequently, it could suppress GC progression and resistance to chemotherapy. The GC patients with senescent CAFs were significantly correlated with poor histologic response to chemotherapy. Conclusions: In this study, we are convinced that the chemotherapy-induced senescence of CAFs could have a significant effect on progression and resistance to chemotherapy in GC.
Inhibitory drugs for chemotherapy-induced senescence of CAFs could be used to overcome the CAF-induced resistance to chemotherapy in GCs.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE316nnn/GSE316370 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE316370 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1402384 ncbi.nlm.nih.gov/bioproject/PRJNA1402384 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by array · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65%
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE316370 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:cancer | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-array | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |