دورية أكاديمية
أعرض في EDS

Combination of clotam and vincristine enhances anti-proliferative effect in medulloblastoma cells.

التفاصيل البيبلوغرافية
العنوان: Combination of clotam and vincristine enhances anti-proliferative effect in medulloblastoma cells.
المؤلفون: Patil S; Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA., Sankpal UT; Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, TX 76107, USA., Hurtado M; Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA., Bowman WP; Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, TX 76107, USA; Department of Hematology and Oncology, Cook Children's Medical Center, Fort Worth, TX 76104, USA., Murray J; Department of Hematology and Oncology, Cook Children's Medical Center, Fort Worth, TX 76104, USA., Borgmann K; Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA., Ghorpade A; Graduate School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, TX 76107, USA., Sutphin R; Haley Center for Cancer and Blood Disorders, Arnold Palmer Hospital for Children, Orlando, FL 32806, USA., Eslin D; Haley Center for Cancer and Blood Disorders, Arnold Palmer Hospital for Children, Orlando, FL 32806, USA. Electronic address: Don.Eslin@orlandohealth.com., Basha R; Texas College of Osteopathic Medicine, University of North Texas Health Science Center, Fort Worth, TX 76107, USA; Department of Hematology and Oncology, Cook Children's Medical Center, Fort Worth, TX 76104, USA. Electronic address: Riyaz.Basha@unthsc.edu.
المصدر: Gene [Gene] 2019 Jul 15; Vol. 705, pp. 67-76. Date of Electronic Publication: 2019 Apr 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier/North-Holland Country of Publication: Netherlands NLM ID: 7706761 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0038 (Electronic) Linking ISSN: 03781119 NLM ISO Abbreviation: Gene Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam, Elsevier/North-Holland, 1976-
مواضيع طبية MeSH: Antineoplastic Combined Chemotherapy Protocols/*pharmacology , Cerebellar Neoplasms/*metabolism , Medulloblastoma/*metabolism , Survivin/*metabolism , Vincristine/*pharmacology , ortho-Aminobenzoates/*pharmacology, Cell Cycle/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Cerebellar Neoplasms/drug therapy ; Dose-Response Relationship, Drug ; Down-Regulation ; Drug Synergism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Inhibitory Concentration 50 ; Medulloblastoma/drug therapy
مستخلص: Medulloblastoma (MB) is characterized by highly invasive embryonal neuro-epithelial tumors that metastasize via cerebrospinal fluid. MB is difficult to treat and the chemotherapy is associated with significant toxicities and potential long-term disabilities. Previously, we showed that small molecule, clotam (tolfenamic acid: TA) inhibited MB cell proliferation and tumor growth in mice by targeting, survivin. Overexpression of survivin is associated with aggressiveness and poor prognosis in several cancers, including MB. The aim of this study was to test combination treatment involving Vincristine® (VCR), a standard chemotherapeutic drug for MB and TA against MB cells. DAOY and D283 MB cells were treated with 10 μg/mL TA or VCR (DAOY: 2 ng/mL; D283: 1 ng/mL) or combination (TA + VCR). These optimized doses were lower than individual IC 50 values. The effect of single or combination treatment on cell viability (CellTiterGlo kit), Combination Index (Chou-Talalay method based on median-drug effect analysis), activation of apoptosis and cell cycle modulation (by flow cytometry using Annexin V and propidium iodide respectively) and the expression of associated markers including survivin (Western immunoblot) were determined. Combination Index showed moderate synergistic cytotoxic effect in both cells. When compared to individual agents, the combination of TA and VCR increased MB cell growth inhibition, induced apoptosis and caused cell cycle (G 2 /M phase) arrest. Survivin expression was also decreased by the combination treatment. TA is effective for inducing the anti-proliferative response of VCR in MB cells. MB has four distinct genetic/molecular subgroups. Experiments were conducted with MB cells representing two subgroups (DAOY: SHH group; D283: group 4/3). TA-induced inhibition of survivin expression potentially destabilizes mitotic microtubule assembly, sensitizing MB cells and enhancing the efficacy of VCR.
(Copyright © 2019. Published by Elsevier B.V.)
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معلومات مُعتمدة: R24 HD000836 United States HD NICHD NIH HHS; S21 MD012472 United States MD NIMHD NIH HHS; U54 MD006882 United States MD NIMHD NIH HHS; Z01 HD008836 United States ImNIH Intramural NIH HHS
فهرسة مساهمة: Keywords: Combination Index; Medulloblastoma; Survivin expression; Tolfenamic acid; Vincristine
المشرفين على المادة: 0 (BIRC5 protein, human)
0 (Survivin)
0 (ortho-Aminobenzoates)
3G943U18KM (tolfenamic acid)
5J49Q6B70F (Vincristine)
تواريخ الأحداث: Date Created: 20190417 Date Completed: 20190610 Latest Revision: 20210109
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC6594553
DOI: 10.1016/j.gene.2019.04.037
PMID: 30991098
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-0038
DOI:10.1016/j.gene.2019.04.037