Molecular Mechanisms of Apoptosis Activation by Heat Shock in Multidrug-Resistant Chinese Hamster Cells
Bibliographic record
Abstract
Multidrug resistance (MDR) is a major obstacle to the success of chemotherapy in cancer treatment and is associated with overexpression of P-glycoprotein. MDR cells, aside from resistance to chemotherapy, might also inhibit apoptosis at various levels in the death signaling pathways. Currently, hyperthermia is used in cancer treatment to sensitize tumor cells to radiation and/or chemotherapy. This study investigated the induction of death receptor and mitochondria-mediated signaling pathways of apoptosis by hyperthermia (41-43 degrees C) in MDR CHRC5 cells compared to drug-sensitive AuxB1 Chinese hamster ovary cells. In the receptor-mediated pathway, CHRC5 cells exhibited higher levels of c-FLIP and lower caspase 8 and caspase 10 activation in response to hyperthermia. In the mitochondria-mediated pathway of heat-induced apoptosis, CHRC5 cells showed higher mitochondrial levels of Bax and tBid, more pronounced mitochondrial membrane depolarization, and increased Apaf-1. Similar levels of caspase 3 activation and cleavage of caspase substrates occurred, showing that overall, CHRC5 cells are not resistant to hyperthermia-induced apoptosis compared to AuxB1 cells. This study reveals for the first time the molecular mechanisms of hyperthermia-induced apoptosis in MDR cells overexpressing P-glycoprotein. CHRC5 and AuxB1 cells showed similar clonogenic survival responses to heat, which implies that hyperthermia could be a promising strategy for eradicating MDR tumor cells in the clinic.
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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 | 0.001 |
| 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".