title: In vitro and in vivo studies of antitumor effects of the recombinant immunotoxin MSH-PE38KDEL on melanoma.
abstract: MSH-PE38KDEL is a chimeric molecule composed of MSH, and fused to a truncated mutant form of Pseudomonas exotoxin (PE38KDEL). Our study aims to evaluate the specific cytotoxicity of recombinant immunotoxin MSH-PE38KDEL on melanoma cells A875 and B16 in vitro, as well as its inhibition of metastatic melanoma in vivo. MSH-PE38KDEL was expressed in Escherichia coli, and greater than 90% purity was obtained. The purified MSH-PE38KDEL was found to be selectively cytotoxic to MSH receptor-positive melanoma cells in vitro. The specific cytotoxicity of recombinant MSH-PE38KDEL to A875 and B16 was over 85% by cell viability assay; however, MSH-PE38KDEL had no cytotoxicity to the human 2BS cells. The anti-tumor activity of MSH-PE38KDEL was evaluated in mice with induced melanoma through intra-tumor or intravenous administration. The results showed that 90% melanoma growths were inhibited, and 40% of the tumors were disappeared completely. Histopathology results showed MSH-PE38KDEL can effectively inhibit intrahepatic metastasis. In conclusion, MSH-PE38KDEL had cytotoxic effects on MSH receptor-positive melanoma cells, and causes significant tumor growth inhibition. These results support a possible new approach for the treatment of melanoma.
authors.forename: Q
authors.initials: Q
authors.lastname: Hui
authors.forename: J
authors.initials: J
authors.lastname: Ma
authors.forename: J
authors.initials: J
authors.lastname: Song
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
authors.forename: H
authors.initials: H
authors.lastname: Ren
authors.forename: W
authors.initials: W
authors.lastname: Jiang
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: D
authors.initials: D
authors.lastname: Guo
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Lu
mesh_terms: D036002:ADP Ribose Transferases / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001427:Bacterial Toxins / Q000627:therapeutic use*; D005098:Exotoxins / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D000922:Immunotoxins / Q000627:therapeutic use*; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000556:secondary; D009074:Melanocyte-Stimulating Hormones / Q000276:immunology*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured; D037521:Virulence Factors / Q000627:therapeutic use*; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; D009074:Melanocyte-Stimulating Hormones; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A