دورية أكاديمية
Rapamycin Suppresses Tumor Growth and Alters the Metabolic Phenotype in T-Cell Lymphoma.
| العنوان: | Rapamycin Suppresses Tumor Growth and Alters the Metabolic Phenotype in T-Cell Lymphoma. |
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| المؤلفون: | Kittipongdaja W; Departments of Dermatology, Medical College of Wisconsin, Milwaukee, USA., Wu X; Departments of Dermatology, Medical College of Wisconsin, Milwaukee, USA., Garner J; Departments of Dermatology, Medical College of Wisconsin, Milwaukee, USA., Liu X; Departments of Dermatology, Medical College of Wisconsin, Milwaukee, USA., Komas SM; Department of Biophysics, Medical College of Wisconsin, Milwaukee, WI, USA., Hwang ST; Departments of Dermatology, Medical College of Wisconsin, Milwaukee, USA., Schieke SM; Departments of Dermatology, Medical College of Wisconsin, Milwaukee, USA. Electronic address: sschieke@mcw.edu. |
| المصدر: | The Journal of investigative dermatology [J Invest Dermatol] 2015 Sep; Vol. 135 (9), pp. 2301-2308. Date of Electronic Publication: 2015 Apr 21. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 0426720 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-1747 (Electronic) Linking ISSN: 0022202X NLM ISO Abbreviation: J Invest Dermatol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2016- : New York : Elsevier Original Publication: Baltimore, Williams & Wilkins. |
| مواضيع طبية MeSH: | Gene Expression Regulation, Neoplastic*, Glycolysis/*drug effects , Sirolimus/*pharmacology , TOR Serine-Threonine Kinases/*genetics, Animals ; Cell Line, Tumor/drug effects ; Cell Proliferation/drug effects ; Disease Models, Animal ; Heterografts ; Humans ; Lymphoma, T-Cell/drug therapy ; Lymphoma, T-Cell/genetics ; Mice ; Mice, Inbred C57BL ; Molecular Targeted Therapy/methods ; Oxidative Phosphorylation/drug effects ; Phenotype ; Sensitivity and Specificity ; TOR Serine-Threonine Kinases/drug effects |
| مستخلص: | The mTOR pathway is a master regulator of cellular growth and metabolism. The biosynthetic and energetic demand of rapidly proliferating cells such as cancer cells is met by metabolic adaptations such as an increased glycolytic rate known as the Warburg effect. Herein, we characterize the anti-tumor effect of rapamycin in a mouse model of T-cell lymphoma and examine the metabolic effects in vitro. The murine T-cell lymphoma line, MBL2, and human cutaneous T-cell lymphoma (CTCL) lines, HH and Hut78, were used in syngeneic or standard NSG mouse models to demonstrate a marked suppression of tumor growth by rapamycin accompanied by inhibition of mTORC1/2. Analysis of the metabolic phenotype showed a substantial reduction in the glycolytic rate and glucose utilization in rapamycin-treated lymphoma cells. This was associated with reduced expression of glucose transporters and glycolytic enzymes in cultured cells and xenograft tumors. As a result of the decrease in glycolytic state, rapamycin-treated cells displayed reduced sensitivity to low-glucose conditions but continued to rely on mitochondrial oxidative phosphorylation (OXPHOS) with sensitivity to inhibition of OXPHOS. Taken together, we demonstrate that rapamycin suppresses growth of T-cell lymphoma tumors and leads to a reduction in aerobic glycolysis counteracting the Warburg effect of cancer cells. |
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| المشرفين على المادة: | EC 2.7.1.1 (mTOR protein, mouse) EC 2.7.11.1 (TOR Serine-Threonine Kinases) W36ZG6FT64 (Sirolimus) |
| تواريخ الأحداث: | Date Created: 20150422 Date Completed: 20151117 Latest Revision: 20211203 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1038/jid.2015.153 |
| PMID: | 25897830 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1523-1747 |
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| DOI: | 10.1038/jid.2015.153 |