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Combination treatment with perifosine and MEK-162 demonstrates synergism against lung cancer cells in vitro and in vivo.
- Source :
-
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine [Tumour Biol] 2015 Jul; Vol. 36 (7), pp. 5699-706. Date of Electronic Publication: 2015 Feb 20. - Publication Year :
- 2015
-
Abstract
- Lung cancer is a global health problem. The search for new therapeutic approaches for the treatment of lung cancer is important. Here, we reported that the AKT inhibitor perifosine and the MEK\ERK inhibitor MEK-162 synergistically induced lung cancer cell (A549 and H460 lines) growth inhibition and apoptosis. The combined efficiency was significantly higher than either agent alone. For the molecular study, perifosine and MEK-162 worked together to concurrently block AKT, mammalian target of rapamycin (mTOR) complex 1 (mTORC1), and MEK-ERK signalings in lung cancer cells, while either agent alone only affected one or two signalings with lower efficiency. In vivo, MEK-162 and perifosine co-administration dramatically inhibited A549 lung cancer xenograft growth, without inducing apparent toxicities. The synergistic activity in vivo was again superior than either agent alone. Thus, perifosine and MEK-162 combination is biologically plausible by acting through effects on different proliferation and survival-related signaling pathways. Our in vitro and in vivo results support the feasibility of investigating the synergism regimen in clinical tests.
- Subjects :
- Animals
Cell Line, Tumor
Cell Proliferation drug effects
Combined Modality Therapy
Drug Synergism
Humans
Lung Neoplasms genetics
Lung Neoplasms pathology
MAP Kinase Kinase Kinases antagonists & inhibitors
Mice
Phosphorylcholine administration & dosage
Proto-Oncogene Proteins c-akt antagonists & inhibitors
Signal Transduction drug effects
Xenograft Model Antitumor Assays
Apoptosis drug effects
Lung Neoplasms drug therapy
Phosphorylcholine analogs & derivatives
Protein Kinase Inhibitors administration & dosage
Proto-Oncogene Proteins c-akt genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0380
- Volume :
- 36
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25697899
- Full Text :
- https://doi.org/10.1007/s13277-015-3244-2