Antitumor effect of a selective COX-2 inhibitor, celecoxib, may be attributed to angiogenesis inhibition through modulating the PTEN/PI3K/Akt/HIF-1 pathway in an H22 murine hepatocarcinoma model
Bibliographic record
Abstract
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has recently been shown to affect the development of different types of cancer. The present study utilized a murine H22 hepatocarcinoma model to investigate the molecular mechanisms involved in celecoxib-induced inhibition of tumor angiogenesis. Tumor-bearing mice were randomly divided into five groups: i) control; ii) low-dose celecoxib (50 mg/kg); iii) high-dose celecoxib (200 mg/kg); iv) 5-fluorouracil (5-FU), (20 mg/kg) and v) combination of 5-FU and celecoxib (50 mg/kg). The antitumor effect of celecoxib was determined by measuring tumor volume. Tumor angiogenesis was evaluated by microvessel density (MVD). Tumor histology and immunostaining for CD34 in endothelial cells were performed to detect MVD. The expression levels of phosphatase and tensin homologue deleted from chromosome 10 (PTEN), phosphatidylinositol 3-kinase (PI3K), phospho‑Akt (P-Akt), COX-2, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A) were detected by ELISA, immunohistochemistry and western blotting, respectively. We discovered substantial growth delay in murine H22 hepatoma as a result of celecoxib treatment. The inhibition rate of tumor growth induced by high-dose and low-dose celecoxib was 49.3 and 37.0%, respectively (P<0.05). The expression of PI3K, P-Akt, COX-2, HIF-1α, VEGF-A and PTEN in tumor tissues treated with celecoxib was demonstrated by immunohistochemistry, and the MVD was decreased in a dose-dependent manner (P<0.05). Reduced PI3K and P-Akt was particularly apparent in the high-dose celecoxib group (P<0.05). ELISA and western blotting data showed that the expression of PI3K, P-Akt, COX-2, HIF-1α and VEGF-A were reduced and PTEN was increased after treatment with celecoxib. In conclusion, the impact of celecoxib-induced tumor growth delay of murine H22 hepatocarcinoma may correlate with the inhibition of angiogenesis by reducing PI3K, P-Akt, COX-2, HIF-1α and VEGF-A expression and increasing PTEN expression in tumor tissue.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".