title: In vitro study on blocking mTOR signaling pathway in EGFR-TKI resistance NSCLC.
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.
authors: Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.
authors: Xu-Dong
authors: XD
authors: Xiang
authors: Department of Gynecologic Oncology, Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.
authors: Jing
authors: J
authors: Yu
authors: Department of Thoracic Surgery, Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China. Electronic address: 15969591603@139.com.
authors: Gao-Feng
authors: GF
authors: Li
authors: Department of Medical Oncology, Third Affiliated Hospital of Kunming Medical University, Kunming 650118, China.
authors: Lin
authors: L
authors: Xie
authors: Kunming Medical University, Kunming 650118, China.
authors: Heng
authors: H
authors: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000068338:Everolimus; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D000068338:Everolimus; C546842:MTOR protein, human; D066246:ErbB Receptors; D058570:TOR Serine-Threonine Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020123:Sirolimus
keywords: EGFR; Everolimus; NSCLC; Targeted therapy; mTOR