The novel fusion proteins, GnRH-p53 and GnRHIII-p53, expression and their anti-tumor effect.
p53, one of the most well studied tumor suppressor factor, is responsible to a variety of damage owing to the induction of apoptosis and cell cycle arrest in the tumor cells. More than 50% of human tumors contain mutation or deletion of p53. Gonadotrophin-releasing hormone (GnRH), as the ligand of Gonadotrophin-releasing hormone receptor (GnRH-R), was used to deliver p53 into tumor cells. The p53 fusion proteins GnRH-p53 and GnRH iii-p53 were expressed and their targeted anti-tumor effects were determined. GnRH mediates its fusion proteins transformation into cancer cells. The intracellular delivery of p53 fusion proteins exerted the inhibition of the growth of H1299 cells in vitro and the reduction of tumor volume in vivo. Their anti-tumor effect was functioned by the apoptosis and cell cycle arrest induced by p53. Hence, the fusion protein could be a novel protein drug for anti-tumor therapy.
Beijing Institute of Pharmacology and Toxicology, Beijing, China.
Peiyuan
P
Jia
Yu
Y
Zhao
Shaoping
S
Wu
Junhua
J
Wu
Shan
S
Gao
Ying
Y
Tong
Yuxia
Y
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D009154:Mutation; D010539:Permeability; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives*; D011966:Receptors, LHRH / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
D011966:Receptors, LHRH; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; C448022:gonadotropin-releasing hormone-III; D007987:Gonadotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid