Hypoxia Induced Resistance to Doxorubicin in Prostate Cancer Cells is Inhibited by Low Concentrations of Glyceryl Trinitrate
Bibliographic record
Abstract
PURPOSE: Tumor hypoxia has been correlated with metastasis and resistance to chemotherapy. Hypoxia is also associated with human prostate cancers, which are highly resistant to chemotherapy. We hypothesized that hypoxia contributes to chemoresistance in prostate cancer cells and this hypoxia induced chemoresistance can be inhibited by low concentrations of nitric oxide (NO) mimetics. MATERIALS AND METHODS: Human PC-3 and mouse TRAMP-C2 prostatic adenocarcinoma cells were incubated in 20% or 0.5% O(2) for 12 hours with or without glyceryl trinitrate (GTN) (0.1 nM). This treatment was followed by a 1-hour incubation with doxorubicin and survival was assessed by clonogenic assays. Western blot analysis was used to measure NO synthase levels. The effect of hypoxia and GTN on cell cycle distribution was determined by flow cytometry. RESULTS: Hypoxic pre-incubation of the 2 cell lines resulted in increased survival following exposure to doxorubicin. Co-incubation of PC-3 and TRAMP-C2 cells with GTN (0.1 nM) inhibited the hypoxia induced resistance to doxorubicin. Each cell line expressed all 3 NO synthase isoforms at levels that were not significantly affected by O(2) concentrations. Cell cycle analysis revealed that there was no significant difference in the distribution of PC-3 cells at each stage of the cycle. However, incubation under hypoxia resulted in a small decrease in the number of TRAMP-C2 cells in S-phase. CONCLUSIONS: These findings indicate that NO may have an important role in the regulation of chemosensitivity in prostate cancer cells. Furthermore, the results suggest that GTN administration may represent a means of chemosensitizing prostatic carcinomas.
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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) | 0.000 | 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".