Effects of combining rapamycin and resveratrol on apoptosis and growth of TSC2-deficient xenograft tumors.
Am J Respir Cell Mol Biol
; 53(5): 637-46, 2015 Nov.
Article
en En
| MEDLINE
| ID: mdl-25844891
ABSTRACT
Lymphangioleiomyomatosis (LAM) is a rare neoplastic metastatic disease affecting women of childbearing age. LAM is caused by hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) as a consequence of tuberous sclerosis complex (TSC) 1/2 inactivation. Clinically, LAM results in cystic lung destruction. mTORC1 inhibition using rapamycin analogs (rapalogs) is partially effective in reducing disease progression and improving lung function. However, cessation of treatment results in continued progression of the disease. In the present study, we investigated the effectiveness of the combination of rapamycin treatment with resveratrol, an autophagy inhibitor, in the TSC2-null xenograft tumor model. We determined that this combination inhibits phosphatidylinositol-4,5-bisphosphate 3-kinase PI3K/Akt/mTORC1 signaling and activates apoptosis. Therefore, the combination of rapamycin and resveratrol may be an effective clinical strategy for treatment of LAM and other diseases with mTORC1 hyperactivation.
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Banco de datos:
MEDLINE
Asunto principal:
Estilbenos
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Neoplasias Uterinas
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Regulación Neoplásica de la Expresión Génica
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Linfangioleiomiomatosis
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Sirolimus
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Proteínas Supresoras de Tumor
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Antineoplásicos
Idioma:
En
Año:
2015
Tipo del documento:
Article