title: Binding Specificity of Radiolabeled Cyclic Peptide 153Sm-DTPA-c(CGRRAGGSC) to MHCC97-H Human Liver Cancer Cells and its Antitumor Effects in vivo.
abstract: This objective of this study is to investigate the effects of the radiolabeled cyclic peptide153Sm-DTPA-c(CGRRAGGSC) on MHCC97-H human liver cancer cells in vitro and in vivo.
  
  
  
  The protein expression levels were examined by Western blot analysis. Biological activity of153Sm-DTPA-c(CGRRAGGSC) was assessed with the radioligand binding assay and competitive inhibition experiment. Subcellular localization of the cyclic peptide was observed by fluorescence microscopy. Animals were implanted with MHCC97-H cells and administered with153Sm-DTPA-c(CGRRAGGSC). Hematoxylin and eosin staining, electron microscopy, and immunohistochemistry were performed to evaluate the effects of153Sm-DTPA-c(CGRRAGGSC) on implanted tumors.
  
  
  
  The expression levels of interleukin 11 receptor were significantly elevated, by 2-to 5-fold, in tumor cell lines, especially for MHCC97-H cells. Characterization of153Sm-DTPA-c(CGRRAGGSC) showed that the biological activity of the cyclic peptide was not altered after labeling, and the radiolabeled cyclic peptide exhibited sufficient binding affinity to interleukin 11 receptor . The cyclic peptide of c(CGRRAGGSC) was mainly distributed in the cytoplasm and on the cell membrane of MHCC97-H cells. The in vivo experiments showed that the tumor growth was significantly inhibited by the treatment of153Sm-DTPA-c(CGRRAGGSC). The inhibitory effect of153Sm-DTPA-c(CGRRAGGSC) on tumor growth was further confirmed by Hematoxylin and eosin staining, electron microscopy, and immunohistochemistry. Moreover, the expression levels of interleukin 11 receptor in implanted tumors were significantly decreased in the treatment groups.
  
  
  
  153Sm-DTPA-c (CGRRAGGSC) could specifically bind to interleukin 11 receptor on MHCC97-H liver tumor cells, inhibiting the cell proliferation and inducing cellular apoptosis. These findings provide experimental evidence for the development of individual treatment of liver cancers, as well as recurrence and metastasis.
authors.affiliation: Department of Radiology, the Third Affiliated Hospital of Nantong University, Wuxi, Jiangsu, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Radiology, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Radiology, the Third Affiliated Hospital of Nantong University, Wuxi, Jiangsu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gu
authors.affiliation: Department of Radiology, the Third Affiliated Hospital of Nantong University, Wuxi, Jiangsu, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Interventional Radiology, the Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Interventional Radiology, the Affiliated Hospital of Guiyang Medical College, Guiyang, Guizhou, China shizhou64@163.com.
authors.forename: Shi
authors.initials: S
authors.lastname: Zhou
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D004369:Pentetic Acid / Q000008:administration & dosage*; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D011868:Radioisotopes / Q000008:administration & dosage*; D053702:Receptors, Interleukin-11 / Q000378:metabolism; D012493:Samarium / Q000008:administration & dosage*; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D011868:Radioisotopes; D053702:Receptors, Interleukin-11; D012493:Samarium; D004369:Pentetic Acid
keywords: 
  153Sm-DTPA-c(CGRRAGGSC); IL 11 analogue; MHCC97-H cells; interleukin 11 receptor (IL-11R); liver cancer