title: A placental growth factor-positively charged peptide potentiates the antitumor activity of interferon-gamma in human brain glioblastoma U87 cells.
abstract: Interferons have been marketed to treat hematological malignancies, but their efficacy in the treatment of solid tumors has been significantly hindered by low antitumor efficacy and numerous side effects. We used a "cDNA in-frame fragment" library screening method to identify short cDNA peptides that potentiate the anti-tumor activity of interferons. In this study, we synthesized a hybrid molecule by fusing a short positively charged peptide derived from placental growth factor-2 to the C-terminus of human IFNγ. Using the human brain glioblastoma U87 cell line as a model system, we found that the hybrid interferon exhibited significantly higher activity than did the wild-type IFNγ in inhibiting tumor cell growth. As compared with the unmodified IFNγ, the hybrid interferon was better at inhibiting cell invasion in a matri-gel assay and at decreasing tumor colony formation. The enhanced antitumor activity of the synthetic interferon was correlated with the activation of interferon pathway genes and the blockade of tumor cell division at the S-G2/M phase. This study demonstrates the potential of a synthetic IFNγ for use as a novel antitumor agent.
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Zhengzhou UniversityZhengzhou 450001, Henan, China; Stanford University Medical School, Palo Alto Veterans Institute for ResearchPalo Alto, CA 94304, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Stem Cell and Cancer Center, First Hospital, Jilin UniversityChangchun, Jilin 130021, China; Stanford University Medical School, Palo Alto Veterans Institute for ResearchPalo Alto, CA 94304, USA.
authors.forename: Naifei
authors.initials: N
authors.lastname: Chen
authors.affiliation: Stem Cell and Cancer Center, First Hospital, Jilin UniversityChangchun, Jilin 130021, China; Stanford University Medical School, Palo Alto Veterans Institute for ResearchPalo Alto, CA 94304, USA.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Yin
authors.affiliation: Stanford University Medical School, Palo Alto Veterans Institute for Research Palo Alto, CA 94304, USA.
authors.forename: Leilei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Stem Cell and Cancer Center, First Hospital, Jilin University Changchun, Jilin 130021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Stem Cell and Cancer Center, First Hospital, Jilin University Changchun, Jilin 130021, China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Wang
authors.affiliation: Stem Cell and Cancer Center, First Hospital, Jilin University Changchun, Jilin 130021, China.
authors.forename: Jiuwei
authors.initials: J
authors.lastname: Cui
authors.affiliation: Department of Neurosurgery, First Affiliated Hospital, Zhengzhou University Zhengzhou 450001, Henan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Stem Cell and Cancer Center, First Hospital, Jilin UniversityChangchun, Jilin 130021, China; Stanford University Medical School, Palo Alto Veterans Institute for ResearchPalo Alto, CA 94304, USA.
authors.forename: Ji-Fan
authors.initials: JF
authors.lastname: Hu
keywords: Antitumor; apoptosis; cell proliferation; interferon-gamma; positively charged peptide; synthetic interferon; tumor