CXCR1 and CXCR2 Antagonism with G31P Attenuates Chemotherapy-Induced Lung Inflammation and Augments the Gefitinib Therapeutic Response in Lung Cancer
Bibliographic record
Abstract
Objectives: Chemotherapy-induced lung inflammation limits the efficacy of anticancer therapies such as gefitinib in non-small cell lung cancer (NSCLC). Glutamic acid-leucine-arginine positive (ELR+) CXC chemokines and their receptors, CXC chemokine receptor 1 and 2 (CXCR1 and CXCR2), mediate both inflammatory responses and tumor progression. This study evaluated the effects of CXCR1/2 antagonism by G31P, a CXC motif chemokine ligand 8 (CXCL8)-mutated peptide, alone or in combination with gefitinib, on lung cancer growth and chemotherapy-induced pulmonary inflammation. Methods: Human NSCLC cell lines (A549 and H460) were treated with gefitinib and/or G31P. Cell proliferation, apoptosis, and signaling pathways, including protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) phosphorylation, were evaluated by cell counting kit-8 (CCK-8) assay, flow cytometry, and Western blotting. An orthotopic lung tumor xenograft model was established in BALB/c nude mice to evaluate tumor growth, metastasis, cytokine expression, and lung histopathology. A bleomycin-induced lung injury model was also used to assess the anti-inflammatory effects of G31P, with or without gefitinib, by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and flow cytometry of inflammatory markers. Results: , G31P with gefitinib significantly suppressed tumor growth, metastasis, and increased apoptosis. G31P decreased CXCL1 and CXCL2, and tumor necrosis factor-alpha (TNF-α) mRNA levels, lung hydroxyproline content, and myeloperoxidase (MPO) activity in the lungs of mice. In the bleomycin-induced lung injury model, G31P similarly reduced inflammatory responses. Conclusion: CXCR1/2 antagonism by G31P attenuates chemotherapy-induced pulmonary inflammation and enhances the anti-tumor efficacy of gefitinib in NSCLC. These findings support the therapeutic potential of G31P as an adjuvant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) to improve clinical outcomes by limiting inflammation.
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 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 | 0.006 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".