title: The anti-tumor effects of the recombinant toxin protein rLj-RGD3 from Lampetra japonica on pancreatic carcinoma Panc-1 cells in nude mice.
abstract: Recombinant Lampetra japonica RGD peptide (rLj-RGD3) is a soluble toxin protein with three RGD (Arg-Gly-Asp) motifs and a molecular weight of 13.5kDa. The aim of this study was to investigate the effects and mechanisms of rLj-RGD3 on tumor growth and survival in pancreatic carcinoma Panc-1 cell-bearing mice. A Panc-1 human pancreatic carcinoma-bearing nude mouse model was successfully generated, and the animals were treated with different doses of rLj-RGD3 for 3 weeks. The volume and weight of the subcutaneous tumors, the survival of the nude mice, histopathological changes, the intratumoral MVD, the number of apoptotic Panc-1 cells, and apoptosis-related proteins and gene expressions were determined. rLj-RGD3 significantly decreased the tumor volumes and weights, and the maximum tumor volume and weight IR values were 53.2% (p<0.001) and 55.9% (p<0.001), respectively. The life expectancy of Panc-1-bearing nude mice treated with rLj-RGD3 was increased by 56.3% (p<0.001). Meanwhile, rLj-RGD3 promoted the expression of Bax, caspase-3, and caspase-9 and inhibited Bcl-2 and VEGF expression. In addition, rLj-RGD3 did not change FAK, PI3K and Akt expression, but p-FAK, p-PI3K and p-Akt, levels were down-regulated. These results show that rLj-RGD3 induced potent anti-tumor activity in vivo and suppressed the growth of transplanted Panc-1 cells in a nude mouse model, implying that rLj-RGD3 may serve as a potent clinical therapeutic agent for human pancreatic carcinoma.
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning Province 116044, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian, Liaoning Province 116029, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning Province 116044, China.
authors.forename: Zuoyu
authors.initials: Z
authors.lastname: Tu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning Province 116044, China.
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning Province 116044, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning Province 116044, China. Electronic address: lv_li@126.com.
authors.forename: Li
authors.initials: L
authors.lastname: Lv
authors.affiliation: School of Life Sciences, Liaoning Normal University, Dalian, Liaoning Province 116029, China. Electronic address: jihongwang999@hotmail.com.
authors.forename: Jihong
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D005397:Fish Venoms / Q000008:administration & dosage* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007798:Lampreys; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009842:Oligopeptides / Q000008:administration & dosage* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000235:genetics
chemical_list: D005397:Fish Venoms; D009363:Neoplasm Proteins; D009842:Oligopeptides; C574387:RGD3 protein, Lampetra japonica; D011994:Recombinant Proteins
keywords: Anti-tumor; Mice; Panc-1 cells; Pancreatic carcinoma; rLj-RGD3