Normoglycemia sensitizes MDA‐MB‐231 breast cancer cells to metformin through an AMPK‐dependent mechanism (LB610)
Bibliographic record
Abstract
Background: Metformin has been shown to have strong anti‐proliferative effect in many breast cancer cell lines, mainly due to the activation of the energy sensing kinase, AMP‐activated protein kinase (AMPK). MDA‐MB‐231 cells are aggressive and invasive breast cancer cells that are known to be resistant to several anti‐cancer agents as well as to the anti‐proliferative effect of metformin. As metformin is a glucose lowering drug, we hypothesized that normoglycemia will sensitize MDA‐MB‐231 cells to the anti‐proliferative effect of metformin. Methods: MDA‐MB‐231 cells were treated with increasing metformin concentrations in hyperglycemic or normoglycemic conditions. The growth inhibitory effect of metformin was assessed by MTT assay. The expression of several proteins involved in cell proliferation was measured by western blotting. Results: In agreement with previous studies, treatment with metformin did not inhibit the growth of MDA‐MB‐231 cells cultured in hyperglycemic conditions. However, metformin significantly inhibited MDA‐MB‐231 growth when the cells were cultured in normoglycemic conditions. In addition, we show that metformin‐treatment of MDA‐MB‐231 cells cultured in normoglycemic conditions and not hyperglycemic conditions caused a striking activation of AMPK, and an AMPK‐dependent inhibition of multiple molecular signaling pathways known to control protein synthesis and cell proliferation. Conclusion: Our data show that normoglycemia sensitizes the triple negative MDA‐MB‐231 breast cancer cells to the anti‐proliferative effect of metformin through an AMPK‐dependent mechanism. These findings suggest that tight normoglycemic control may enhance the anti‐proliferative effect of metformin in diabetic cancer patients. Grant Funding Source : Supported by Canadian Institutes of Health Research and Alberta Innovates ‐ Health Solutions
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".