title: Induction of non-small cell lung carcinoma apoptosis using soluble RGD-TRAIL             by targeting the integrin receptor of tumor cells.
abstract: The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a             promising candidate for cancer therapeutics that exhibits the ability to preferentially             induce apoptosis in malignant cells. RGD peptides bind to the integrins, ανβ3             and ανβ5, which are selectively expressed in tumor neovasculature and at the surface             of certain tumor cells. To enhance the antitumor effect, an RGD-TRAIL protein,             in which TRAIL was fused with the RGD motif-containing cell adhesive sequence,             GRGDNP (gly-arg-gly-asp-asn-pro), was constructed and evaluated for bioactivity.             The soluble TRAIL and RGD-TRAIL proteins were expressed in Escherichia coli BL21             (DE3) and purified using a non-denaturing method. The antitumor effect of the             purified RGD-TRAIL on cell proliferation was evaluated in vitro using MTT and             wound healing assays and cell apoptosis was assessed by Hoechst 33342 staining             and PARP expression analysis. The results revealed that RGD-TRAIL inhibited the             proliferation of multiple tumor cell lines (A549, NCI-H1299 and HCC827). Western             blot analysis demonstrated that the treatment of tumor cells with RGD-TRAIL activated             the apoptotic pathway by the cleavage of PARP, in the same way as wild-type TRAIL             (wtTRAIL). These results demonstrate that RGD-TRAIL possesses more potent antitumor             effects than wtTRAIL and, therefore, merits further investigation in preclinical             and clinical studies.
authors.affiliation: Central Laboratory, Affiliated Hospital of Qingdao University,                     Medical College, Qingdao 266003, P.R. China.
authors.forename: Ruyong
authors.initials: R
authors.lastname: Yao
authors.forename: Aihua
authors.initials: A
authors.lastname: Sui
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Wang
authors.forename: Shihai
authors.initials: S
authors.lastname: Liu
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xiangping
authors.initials: X
authors.lastname: Liu
authors.forename: Haiping
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000633:toxicity; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019030:Receptors, Vitronectin; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C103774:glycyl-arginyl-glycyl-aspartyl-asparaginyl-proline; C064660:integrin alphaVbeta5; C047981:arginyl-glycyl-aspartic acid; D011065:Poly(ADP-ribose) Polymerases