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Tumor Biology

, Volume 36, Issue 7, pp 5699–5706 | Cite as

Combination treatment with perifosine and MEK-162 demonstrates synergism against lung cancer cells in vitro and in vivo

  • Jianli Zhang
  • Yue Hong
  • Jie Shen
Research Article

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.

Keywords

Lung cancer Perifosine MEK-162 PI3K-AKT-mTOR MEK-ERK Synergism 

Abbreviations

ELISA

Enzyme-linked immunosorbent assay

ERK

Extracellular regulated kinase

FBS

Fetal bovine serum

mTOR

Mammalian target of rapamycin

mTORC1

Mammalian target of rapamycin (mTOR) complex 1

NSCLCs

Non-small cell lung cancers

PI3K

Phosphatidylinositol-3-kinase

PVDF

Polyvinylidene fluoride

RCC

Renal cell carcinoma

Notes

Acknowledgments

This work is supported by the National Science Foundation of China.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Respiratory DiseasesThe First Affiliated Hospital of Zhejiang UniversityHangzhouChina
  2. 2.Department of Pediatricsthe First Affiliated Hospital of Zhejiang UniversityHangzhouChina

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