Overexpression of bcl-2 regulates sodium butyrate- and/or docetaxel-induced apoptosis in human bladder cancer cells bothin vitro andin vivo
Bibliographic record
Abstract
Sodium butyrate (NaBt), a physiologically occurring short-chain fatty acid, induces differentiation as well as apoptosis in numerous cell types, and this induction is partially regulated by Bcl-2 expression. The objectives of our study were to characterize the in vitro effects of NaBt and/or docetaxel on the growth, cell cycle and apoptosis of human bladder cancer cells, and to determine whether tumor growth in vivo is inhibited by isobutyramide, an orally bioavailable Bt analogue, and/or docetaxel by using Bcl-2-transfected human bladder cancer cell line KoTCC-1/BH and control vector only-transfected cell line KoTCC-1/C. NaBt caused a decrease in growth of both KoTCC-1/C and KoTCC-1/BH cells, however, its growth inhibitory effect was significantly greater in KoTCC-1/C cells. One mM NaBt resulted in G1 cell cycle arrest, accompanied by up-regulation of p21 (waf1/cip1) and down-regulation of cyclin D1 in KoTCC-1/C cells, whereas KoTCC-1/BH showed resistance to G1 cell cycle arrest. An amount of 5 mM NaBt induced apoptosis, accompanied by up-regulation of Bak in KoTCC-1/C cells but failed to induce apoptosis in KoTCC-1/BH cells despite substantial down-regulation of Bcl-2. Oral administration of isobutyramide significantly reduced the KoTCC-1/C tumor volume compared with the KoTCC-1/BH tumor volume in nude mice. Furthermore, docetaxel induced Bcl-2 phosphorylation in KoTCC-1/BH cells and combined treatment with isobutyramide and docetaxel synergistically inhibited the growth of KoTCC-1/BH cells both in vitro and in vivo. These findings suggest that isobutyramide therapy could be a novel therapeutic strategy for patients with bladder cancer if docetaxel is combined according to the Bcl-2 expression status.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".