Leukemia by increasing BIM expression with the PI3K/mTOR inhibitor BEZ235
نویسندگان
چکیده
Modulation of glucocorticoid resistance in pediatric T-cell Acute Lymphoblastic 1 Leukemia by increasing BIM expression with the PI3K/mTOR inhibitor BEZ235 2 3 Connor P. Hall , C. Patrick Reynolds, Min H. Kang 4 5 Cancer Center, Pharmacology and Neuroscience, Cell Biology & Biochemistry, Pediatrics, 6 Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 7 Lubbock, TX; 8 9 Correspondence: Min H. Kang, PharmD 10 Cell Biology & Biochemistry 11 School of Medicine, Texas Tech University Health Sciences Center 12 3601 4 Street STOP 9445, Lubbock, TX 79430 13 Phone: 806-743-2694; Fax: 806-743-2990 14 Email: [email protected] 15 16
منابع مشابه
Modulation of Glucocorticoid Resistance in Pediatric T-cell Acute Lymphoblastic Leukemia by Increasing BIM Expression with the PI3K/mTOR Inhibitor BEZ235.
PURPOSE The aim of our study is to evaluate the preclinical therapeutic activity and mechanism of action of BEZ235, a dual PI3K/mTOR inhibitor, in combination with dexamethasone in acute lymphoblastic leukemia (ALL). EXPERIMENTAL DESIGN The cytotoxic effects of BEZ235 and dexamethasone as single agents and in combination were assessed in a panel of ALL cell lines and xenograft models. The und...
متن کاملPI3K/mTOR dual inhibitor NVP-BEZ235 decreases Mcl-1 expression and sensitizes ovarian carcinoma cells to Bcl-xL-targeting strategies, provided that Bim expression is induced.
We previously showed that Bcl-xL and Mcl-1 cooperatively protect platinum-resistant ovarian cancer cells from apoptosis. Here we assessed the anticancer potential of combining ABT-737-induced inhibition of Bcl-xL with Mcl-1 inhibition via PI3K/Akt/mTOR pathway disruption using NVP-BEZ235. NVP-BEZ235 inhibited cell proliferation without inducing apoptosis. It strongly repressed Mcl-1 expression ...
متن کاملModulation of glucocorticoid resistance in pediatric T - cell Acute Lymphoblastic 1 Leukemia by increasing BIM expression with the PI 3 K / mTOR inhibitor BEZ 235
Modulation of glucocorticoid resistance in pediatric T-cell Acute Lymphoblastic 1 Leukemia by increasing BIM expression with the PI3K/mTOR inhibitor BEZ235 2 3 Connor P. Hall , C. Patrick Reynolds, Min H. Kang 4 5 Cancer Center, Pharmacology and Neuroscience, Cell Biology & Biochemistry, Pediatrics, 6 Internal Medicine, School of Medicine, Texas Tech University Health Sciences Center, 7 Lubbock...
متن کاملDual inhibition of Bcl-2 and Bcl-xL strikingly enhances PI3K inhibition-induced apoptosis in human myeloid leukemia cells through a GSK3- and Bim-dependent mechanism.
Effects of concomitant inhibition of the PI3K/AKT/mTOR pathway and Bcl-2/Bcl-xL (BCL2L1) were examined in human myeloid leukemia cells. Tetracycline-inducible Bcl-2 and Bcl-xL dual knockdown sharply increased PI3K/AKT/mTOR inhibitor lethality. Conversely, inducible knockdown or dominant-negative AKT increased, whereas constitutively active AKT reduced lethality of the Bcl-2/Bcl-xL inhibitor ABT...
متن کاملTargeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer
BACKGROUND Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro. METHODS In HT-29 and HCT-116 cells, BEZ235, ...
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