NDLI: LKB1 gene inactivation does not sensitize non-small cell lung cancer cells to mTOR inhibitors in vitro.

Please wait, while we are loading the content...

Year: 2017 Volume: 38

Year: 2016 Volume: 37

Year: 2015 Volume: 36

Year: 2015 Volume: 36 Issue: 12

Year: 2015 Volume: 36 Issue: 11

Year: 2015 Volume: 36 Issue: 10

Year: 2015 Volume: 36 Issue: 9

LKB1 gene inactivation does not sensitize non-small cell lung cancer cells to mTOR inhibitors in vitro.

Cathepsin L suppression increases the radiosensitivity of human glioma U251 cells via G2/M cell cycle arrest and DNA damage.

Synergistic suppression of human breast cancer cells by combination of plumbagin and zoledronic acid In vitro.

JNK is required for maintaining the tumor-initiating cell-like properties of acquired chemoresistant human cancer cells

New benzimidazole acridine derivative induces human colon cancer cell apoptosis in vitro via the ROS-JNK signaling pathway.

Discovery and structural optimization of 1-phenyl-3-(1-phenylethyl)urea derivatives as novel inhibitors of CRAC channel

Enhancement of cellular uptake, transport and oral absorption of protease inhibitor saquinavir by nanocrystal formulation.

Landmark studies on the glucagon subfamily of GPCRs: from small molecule modulators to a crystal structure.

Policresulen, a novel NS2B/NS3 protease inhibitor, effectively inhibits the replication of DENV2 virus in BHK-21 cells

Physical performance and life quality in postmenopausal women supplemented with vitamin D: a two-year prospective study

Structural basis for 18-ß-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor.

WSS25, a sulfated polysaccharide, inhibits RANKL-induced mouse osteoclast formation by blocking SMAD/ID1 signaling.

Protease Omi cleaving Hax-1 protein contributes to OGD/R-induced mitochondrial damage in neuroblastoma N2a cells and cerebral injury in MCAO mice.

Year: 2015 Volume: 36 Issue: 8

Year: 2015 Volume: 36 Issue: 7

Year: 2015 Volume: 36 Issue: 6

Year: 2015 Volume: 36 Issue: 5

Year: 2015 Volume: 36 Issue: 4

Year: 2015 Volume: 36 Issue: 3

Year: 2015 Volume: 36 Issue: 2

Year: 2015 Volume: 36 Issue: 1

Year: 2014 Volume: 35

Year: 2013 Volume: 34

Year: 2012 Volume: 33

Year: 2011 Volume: 32

Year: 2010 Volume: 31

Year: 2009 Volume: 30

Year: 2008 Volume: 29

Year: 2007 Volume: 28

LKB1 gene inactivation does not sensitize non-small cell lung cancer cells to mTOR inhibitors in vitro.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Xiao, Ping Sun, Lin-lin Wang, Jing Han, Rui-li Ma, Qing Zhong, Dian-sheng
Description	Country affiliation: China Author Affiliation: Xiao P ( Department of Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.); Sun LL ( Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.); Wang J ( Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.); Han RL ( Department of Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.); Ma Q ( Department of Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.); Zhong DS ( Department of Oncology, Tianjin Medical University General Hospital, Tianjin 300052, China.)
Abstract	AIM: Previous study has shown that endometrial cancers with LKB1 inactivation are highly responsive to mTOR inhibitors. In this study we examined the effect of LKB1 gene status on mTOR inhibitor responses in non-small cell lung cancer (NSCLC) cells. METHODS: Lung cancer cell lines Calu-1, H460, H1299, H1792, and A549 were treated with the mTOR inhibitors rapamycin or everolimus (RAD001). The mTOR activity was evaluated by measuring the phosphorylation of 4EBP1 and S6K, the two primary mTOR substrates. Cells proliferation was measured by MTS or sulforhodamine B assays. RESULTS: The basal level of mTOR activity in LKB1 mutant A549 and H460 cells was significantly higher than that in LKB1 wild-type Calu-1 and H1792 cells. However, the LKB1 mutant A549 and H460 cells were not more sensitive to the mTOR inhibitors than the LKB1 wild-type Calu-1 and H1792 cells. Moreover, knockdown of LKB1 gene in H1299 cells did not increase the sensitivity to the mTOR inhibitors. Treatment with rapamycin or RAD001 significantly increased the phosphorylation of AKT in both LKB1 wild-type and LKB1 mutant NSCLC cells, which was attenuated by the PI3K inhibitor LY294002. Furthermore, RAD001 combined with LY294002 markedly enhanced the growth inhibition on LKB1 wild-type H1792 cells and LKB1 mutant A549 cells. CONCLUSION: LKB1 gene inactivation in NSCLC cells does not increase the sensitivity to the mTOR inhibitors. The negative feedback activation of AKT by mTOR inhibition may contribute to the resistance of NSCLC cells to mTOR inhibitors.
File Format	HTM / HTML
ISSN	16714083
e-ISSN	17457254
DOI	10.1038/aps.2015.19
Journal	Acta Pharmacologica Sinica
Issue Number	9
Volume Number	36
Language	English
Publisher	Macmillan Publishers Limited
Publisher Date	2015-09-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Pharmacology Carcinoma, Non-small-cell Lung Drug Therapy Everolimus Pharmacology Lung Neoplasms Protein Kinase Inhibitors Protein-serine-threonine Kinases Genetics Sirolimus Tor Serine-threonine Kinases Antagonists & Inhibitors Metabolism Pathology Cell Line, Tumor Drug Resistance, Neoplasm Gene Silencing Lung Drug Effects Mutation Phosphatidylinositol 3-kinases Proto-oncogene Proteins C-akt Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Pharmacology Pharmacology (medical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Emerging strategies to overcome the resistance to current mTOR inhibitors in renal cell carcinoma

A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt

Targeting mTOR in mantle cell lymphoma: current and future directions.

MTOR downregulates iodide uptake in thyrocytes.

The PI3K/Akt and mTOR/P70S6K signaling pathways in human uveal melanoma cells: interaction with B-Raf/ERK.

Everolimus in the treatment of hormone receptor-positive breast cancer.

Targeting LKB1 signaling in cancer

Preclinical rationale for PI3K/Akt/mTOR pathway inhibitors as therapy for epidermal growth factor receptor inhibitor-resistant non-small-cell lung cancer.

Akt activation disrupts mammary acinar architecture and enhances proliferation in an mTOR-dependent manner

LKB1 gene inactivation does not sensitize non-small cell lung cancer cells to mTOR inhibitors in vitro.

Similar Documents

Emerging strategies to overcome the resistance to current mTOR inhibitors in renal cell carcinoma

A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt

Targeting mTOR in mantle cell lymphoma: current and future directions.

MTOR downregulates iodide uptake in thyrocytes.

The PI3K/Akt and mTOR/P70S6K signaling pathways in human uveal melanoma cells: interaction with B-Raf/ERK.

Everolimus in the treatment of hormone receptor-positive breast cancer.

Targeting LKB1 signaling in cancer

Preclinical rationale for PI3K/Akt/mTOR pathway inhibitors as therapy for epidermal growth factor receptor inhibitor-resistant non-small-cell lung cancer.

Akt activation disrupts mammary acinar architecture and enhances proliferation in an mTOR-dependent manner

LKB1 gene inactivation does not sensitize non-small cell lung cancer cells to mTOR inhibitors in vitro.