title: rLj-RGD3 induces apoptosis via the mitochondrial-dependent pathway and inhibits adhesion, migration and invasion of human HeyA8 cells via FAK pathway.
abstract: Ovarian carcinoma is a tumor derived from ovary, which brings relatively higher mortality rate among the fatal gynecological cancers. Recently, lots of studies have concentrated on the anti-tumor effects of Arg-Gly-Asp (RGD) motif containing peptides due to their integrin binding properties. In order to meet the criterion of genetic engineering drugs, a recombinant RGD toxin protein (rLj-RGD3) without a His-tag was cloned from the buccal glands of Lampetra japonica in the present study. After endotoxin removal, the His-tag removed rLj-RGD3 was shown to inhibit the proliferation of HeyA8 cells. According to the confocal microscope, flow cytometry and western blot analysis, rLj-RGD3 could trigger HeyA8 cells apoptosis by changing mitochondrial membrane potential, arrangement of F-actin, protein level of BCL2, BAX, caspase 3, and cleaved caspase 3, concentration of cytoplasmic calcium, as well as phosphorylation level of ERK/JNK/p38. Furthermore, rLj-RGD3 was also able to suppress the adhesion, migration, and invasion processes of HeyA8 cells by disturbing the organization of F-actin and reducing the level of p-FAK. In addition, rLj-RGD3 could inhibit the adhesion of HeyA8 cells to extracellular matrix proteins by competitively binding to integrins, indicated that rLj-RGD3 might act as an anti-tumor drug to treat ovarian carcinoma patients in the future.
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian 116081, PR China; Lamprey Research Center, Liaoning Normal University, Dalian 116081, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian 116081, PR China; Lamprey Research Center, Liaoning Normal University, Dalian 116081, PR China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian 116081, PR China; Lamprey Research Center, Liaoning Normal University, Dalian 116081, PR China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Han
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian 116081, PR China; Lamprey Research Center, Liaoning Normal University, Dalian 116081, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Gou
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian 116081, PR China; Lamprey Research Center, Liaoning Normal University, Dalian 116081, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian 116081, PR China; Lamprey Research Center, Liaoning Normal University, Dalian 116081, PR China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Li
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian 116081, PR China; Lamprey Research Center, Liaoning Normal University, Dalian 116081, PR China. Electronic address: liulangmao1980@126.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian 116081, PR China; Lamprey Research Center, Liaoning Normal University, Dalian 116081, PR China. Electronic address: y.y.200@163.com.
authors.forename: Jihong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects*; D009361:Neoplasm Invasiveness; D009842:Oligopeptides / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D011994:Recombinant Proteins; C047981:arginyl-glycyl-aspartic acid; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Anti-tumor; HeyA8 cells; rLj-RGD3