Effects of Combining Rapamycin and Resveratrol on Apoptosis and Growth of TSC2-Deficient Xenograft Tumors

被引：28

作者：

Alayev, Anya ^{[1
]}

Salamon, Rachel S. ^{[1
]}

Sun, Yang ^{[2
,3
]}

Schwartz, Naomi S. ^{[1
]}

Li, Chenggang ^{[2
,3
]}

Yu, Jane J. ^{[2
,3
]}

Holz, Marina K. ^{[4
,5
,6
]}

机构：

[1] Yeshiva Univ, Stern Coll Women, Dept Biol, New York, NY USA

[2] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02115 USA

[3] Harvard Univ, Sch Med, Boston, MA USA

[4] Yeshiva Univ, Dept Biol, New York, NY USA

[5] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA

[6] Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA

来源：

AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY | 2015年 / 53卷 / 05期

基金：

美国国家卫生研究院;

关键词：

rapamycin; resveratrol; LAM; TSC2; mTORC1; TUBEROUS SCLEROSIS COMPLEX; PULMONARY LYMPHANGIOLEIOMYOMATOSIS LAM; PROTEIN S6 PHOSPHORYLATION; SUPPRESSOR GENE; IN-VITRO; TSC2; SIROLIMUS; CELLS; KINASE; CANCER;

D O I：

10.1165/rcmb.2015-0022OC

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：637 / 646

页数：10

共 36 条

[1]

The Combination of Rapamycin and Resveratrol Blocks Autophagy and Induces Apoptosis in Breast Cancer Cells [J].