Antitumor effect of metformin is mediated by AMPK and FOXO3a
Bibliographic record
Abstract
The objective of this study was to analyze the antitumor effect of metformin in‐vitro and in‐vivo. Breast cancer MCF‐7 cells were treated with metformin for 24, 48 and 72h. Antiproliferative activity was analyzed by the MTT assay. Oxidative stress was measured by the CM‐H 2 DCFDA assay. Apoptosis and cell cycle were analyzed by flow cytometry. mRNA expression was determined by RT‐PCR and protein expression by Western Blot. Metformin demonstrated an time‐ and dose‐dependent antiproliferative effect. This effect was associated with an increase in oxidative stress, apoptosis and cell cycle arrest. And, an increase in AMPK and FOXO3a activity was observed. Control and obese rats of 16 weeks of age received Walker‐256 tumor cells(1×10 7 cells/mL, sc) and metformin(300mg/kg, by gavage, for 15d, CTM and OTM). Control rats received tap water (CT and OT). On the 18 th week the tumor development was analyzed. Tumor development was higher in OT rats than compared with CT. Metformin reduced it and increased the pRb and p27 mRNA expression. In conclusion, we demonstrated that metformin has an antitumor effect which was mediated by pRb, p27, AMPK and FOXO3a. Financial support: FAPESP(Brazil), NSERC‐RCD and NOSM(Canada)
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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".