title: Additive effect of TRAIL and p53 gene transfer on apoptosis of human lung cancer cell lines.
abstract: TRAIL is a cytokine that can induce tumor-specific apoptosis through its specific death receptors (DR4 and DR5) and p53 has been proven to increase the expression of death receptors. To examine their interaction in tumor suppression, p53 and TRAIL genes were inserted in recombinant adenovirus vectors and transferred simultaneously into non-small cell lung cancer cell lines (NCI-H157, NCI-H358, NCI-H460 and A549). Western blot assay demonstrated production of TRAIL protein in NCI-H157 and A549 cell lines. Increased expressions of DR4 and DR5 of NCI-H157 and DR4 of A549 after p53 overexpression were confirmed by flow cytometry. p53 or TRAIL gene transfer increased sub-G1 fraction in cell cycle analysis and inhibited the tumor growth dose-dependently and the degree was potentiated by co-transfer. But isobologram analysis indicated an additive effect. Together, these data indicate that p53 and TRAIL interact additively on tumor apoptosis despite theoretical synergism.
authors.affiliation: Department of Internal Medicine and Lung Institute of Medical Research Center, Seoul National University College of Medicine, Clinical Research Institute, Seoul National University Hospital, Seoul, Korea.
authors.forename: Seung Hun
authors.initials: SH
authors.lastname: Jang
authors.forename: Ja Young
authors.initials: JY
authors.lastname: Seol
authors.forename: Cheol Hyeon
authors.initials: CH
authors.lastname: Kim
authors.forename: Chul-Gyu
authors.initials: CG
authors.lastname: Yoo
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Kim
authors.forename: Sung Koo
authors.initials: SK
authors.lastname: Han
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Shim
authors.forename: Choon-Taek
authors.initials: CT
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D005822:Genetic Vectors; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53