In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC

Asian Pac J Trop Med. 2014 May;7(5):394-7. doi: 10.1016/S1995-7645(14)60063-8.

Abstract

Objective: To investigate the effect and mechanism of inhibitor everolimus on EGFR-TKI resistance NSCLC.

Methods: MTT assay was used to detect proliferation of human non-small cell lung cancer cell line A549. Flow cytometry was used to detect the changes of apoptosis and cycle distribution in each group after 24 h and 48 h. RT-PCR was used to detect the changes of PTEN and 4EBP1 expression levels after 48 h of monotherapy and combination therapy.

Results: MTT assay showed that everolimus had dose-dependent inhibition against growth of A549 cells. Flow cytometry showed when everolimus could induce apoptosis and induce G0/G1 phase cell cycle arrest, which was time-dependent (P<0.05). RT-PCR showed everolimus could increase PTEN and 4EBP1 expression.

Conclusions: mTOR inhibitor everolimus has an inhibitory effect on EGFR-TKI resistant NSCLC, which cannot reverse the resistance effect of EGFR-TKI resistant cell line A549. The relationship between EGFR/AKT signaling pathway and the mTOR signaling pathway and the mechanism in non-small cell lung cancer need further study.

Keywords: EGFR; Everolimus; NSCLC; Targeted therapy; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • ErbB Receptors / antagonists & inhibitors*
  • Everolimus
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / metabolism*
  • PTEN Phosphohydrolase / analysis
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Phosphoproteins / analysis
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Signal Transduction / drug effects*
  • Sirolimus / analogs & derivatives
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Phosphoproteins
  • Everolimus
  • MTOR protein, human
  • ErbB Receptors
  • TOR Serine-Threonine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Sirolimus