Open AccessIn vitro and in vivo studies of antitumor effects of the recombinant immunotoxin MSH-PE38KDEL on melanoma
Author(s) -
Hui Qiu,
Jun Ma,
Jing Song,
Z Liu,
Hening Ren,
Wenjie Jiang,
Y Wang,
Ying Xu,
Dadong Guo,
X Zhang,
Shuaiyao Lu
Publication year - 2014
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2014_048
Subject(s) - pseudomonas exotoxin , melanoma , cytotoxicity , immunotoxin , in vitro , in vivo , cytotoxic t cell , recombinant dna , cancer research , chemistry , microbiology and biotechnology , medicine , biology , biochemistry , gene
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.