Excel · study · 2026
Fluvastatin plus dipyridamole suppresses canine hemangiosarcoma growth in patient-derived xenograft models through lactate dehydrogenase-associated cholesterol/lipid metabolism
Listed in NCBI GEO
Tumor cells exhibit distinct metabolic features such as the Warburg effect, consuming abundant glucose and producing large amounts of lactate even under aerobic conditions.
Description
Lactate dehydrogenase (LDH) plays a central role in regulating the intracellular lactate levels. Canine hemangiosarcoma (HSA) is a highly aggressive malignant tumor arising from vascular endothelial cells, and no effective targeted therapies have been established due to limited understanding of its molecular pathogenesis.
The endothelial cells also rely on glycolysis for energy sources, although the involvement of lactate and LDH in HSA remains unknown. In this study, we investigated the role of lactate metabolism and LDH in HSA. The dual LDHA/LDHB inhibitor (R)-GNE-140 significantly suppressed HSA cell proliferation in vitro and reduced the expression of cholesterol-related genes.
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Knockout experiments showed that loss of LDHA, but not LDHB, was associated with decreased expression of cholesterol-related genes and reduced lipid droplet formation in HSA cells. Based on the association, we tested fluvastatin with or without dipyridamole to evaluate their anti-tumor efficacy using PDX models. While fluvastatin monotherapy had limited effect, the combined treatment significantly inhibited tumor growth.
These findings suggest that LDH may link to cholesterol metabolism and that cholesterol pathway inhibition could offer a therapeutic opportunity in HSA.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE314nnn/GSE314239 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314239 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1390509 ncbi.nlm.nih.gov/bioproject/PRJNA1390509 ↗
project · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing
- From keywords
- Life Sciences
- Inferred from text
- Cancer 65%
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE314239 | 15 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-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| 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 |