دورية أكاديمية
Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells.
| العنوان: | Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells. |
|---|---|
| المؤلفون: | Matos BS; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal.; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal., Peixoto da Silva S; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal.; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal.; Department of Biological Sciences, FFUP - Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal., Vasconcelos MH; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal.; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal.; Department of Biological Sciences, FFUP - Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira 228, Porto 4050-313, Portugal., Xavier CPR; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal.; Cancer Drug Resistance Group, IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Rua Alfredo Allen 208, Porto 4200-135, Portugal.; UCIBIO - Applied Molecular Biosciences Unit, Toxicologic Pathology Research Laboratory, University Institute of Health Sciences (1H-TOXRUN, IUCS-CESPU), Gandra 4585-116, Portugal.; Associate Laboratory i4HB - Institute for Health and Bioeconomy, University Institute of Health Sciences - CESPU, Gandra 4585-116, Portugal. |
| المصدر: | Cancer drug resistance (Alhambra, Calif.) [Cancer Drug Resist] 2024 May 20; Vol. 7, pp. 19. Date of Electronic Publication: 2024 May 20 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: OAE Publishing Inc Country of Publication: United States NLM ID: 101738710 Publication Model: eCollection Cited Medium: Internet ISSN: 2578-532X (Electronic) Linking ISSN: 2578532X NLM ISO Abbreviation: Cancer Drug Resist Subsets: PubMed not MEDLINE |
| أسماء مطبوعة: | Original Publication: Alhambra, CA : OAE Publishing Inc., 2018- |
| مستخلص: | Aim: Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of pentoxifylline, an anti-fibrotic and chitinase 3-like-1 (CHI3L1) inhibitor drug, with conventional chemotherapy to improve NSCLC treatment. Methods: The effect of pentoxifylline in the expression levels of P-glycoprotein (P-gp), CHI3L1 and its main downstream proteins, as well as on cell death, cell cycle profile, and P-gp activity was studied in two pairs of sensitive and MDR counterpart NSCLC cell lines (NCI-H460/NCI-H460/R and A549/A549-CDR2). Association studies between CHI3L1 gene expression and NSCLC patients' survival were performed using The Cancer Genome Atlas (TCGA) analysis. The sensitizing effect of pentoxifylline to different drug regimens was evaluated in both sensitive and MDR NSCLC cell lines. The cytotoxicity of the drug combinations was assessed in MCF10A non-tumorigenic cells. Results: Pentoxifylline slightly decreased the expression levels of CHI3L1, β-catenin and signal transducer and activator of transcription 3 (STAT3), and caused a significant increase in the G1 phase of the cell cycle in both pairs of NSCLC cell lines. A significant increase in the % of cell death was observed in the sensitive NCI-H460 cell line. TCGA analysis revealed that high levels of CHI3L1 are associated with low overall survival (OS) in NSCLC patients treated with vinorelbine. Moreover, pentoxifylline sensitized both pairs of sensitive and MDR NSCLC cell lines to the different drug regimens, without causing significant toxicity to non-tumorigenic cells. Conclusion: This study suggests the possibility of combining pentoxifylline with chemotherapy to increase NSCLC therapeutic response, even in cases of MDR. Competing Interests: Xavier CPR is a Junior Editorial Board Member of the journal Cancer Drug Resistance, while the other authors have declared that they have no conflicts of interest. (© The Author(s) 2024.) |
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| فهرسة مساهمة: | Keywords: Chitinase 3-like-1; combined therapies; drug repurposing; multidrug resistance; non-small cell lung cancer; pentoxifylline |
| تواريخ الأحداث: | Date Created: 20240605 Latest Revision: 20240607 |
| رمز التحديث: | 20240607 |
| مُعرف محوري في PubMed: | PMC11149106 |
| DOI: | 10.20517/cdr.2024.04 |
| PMID: | 38835347 |
| قاعدة البيانات: | MEDLINE |
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