title: TRAIL-coated lipid-nanoparticles overcome resistance to soluble recombinant TRAIL in non-small cell lung cancer cells.
abstract: OBJECTIVE
  Non-small cell lung cancer (NSCLC) is one the types of cancer with higher prevalence and mortality. Apo2-Ligand/TRAIL is a TNF family member able to induce apoptosis in tumor cells but not in normal cells. It has been tested in clinical trials against different types of human cancer including NSCLC. However, results of clinical trials have shown a limited efficacy of TRAIL-based therapies. Recently we have demonstrated that artificial lipid nanoparticles coated with bioactive Apo2L/TRAIL (LUV-TRAIL) greatly improved TRAIL cytotoxic ability being capable of killing chemoresistant hematological cancer cells. In the present work we have extended the study to NSCLC.
  
  
  METHODS
  LUV-TRAIL-induced cytotoxicity was assessed on different NSCLC cell lines with different sensitivity to soluble TRAIL and on primary human tumor cells from three patients suffering from NSCLC cancer. We also tested LUV-TRAIL-cytotoxic ability in combination with several anti-tumor agents.
  
  
  RESULTS
  LUV-TRAIL exhibited a greater cytotoxic effect compared to soluble TRAIL both in A549 cells and primary human NSCLC cells. LUV-TRAIL-induced cell death was dependent on caspase-8 and caspase-3 activation. Moreover, combination of LUV-TRAIL with other anti-tumor agents such as flavopiridol, and SNS-032 clearly enhanced LUV-TRAIL-induced cytotoxicity against NSCLC cancer cells.
  
  
  CONCLUSIONS
  The novel formulation of TRAIL based on displaying it on the surface of lipid nanoparticles greatly increases its anti-tumor activity and has clinical potential in cancer treatment.
authors.affiliation: Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Spain.
authors.forename: Diego
authors.initials: D
authors.lastname: De Miguel
authors.forename: Ana
authors.initials: A
authors.lastname: Gallego-Lleyda
authors.forename: José María
authors.initials: JM
authors.lastname: Ayuso
authors.forename: Sandra
authors.initials: S
authors.lastname: Erviti-Ardanaz
authors.forename: Roberto
authors.initials: R
authors.lastname: Pazo-Cid
authors.forename: Celia
authors.initials: C
authors.lastname: del Agua
authors.forename: Luis José
authors.initials: LJ
authors.lastname: Fernández
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ochoa
authors.forename: Alberto
authors.initials: A
authors.lastname: Anel
authors.forename: Luis
authors.initials: L
authors.lastname: Martinez-Lostao
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008081:Liposomes; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8