Anti-tumor effects of P-LPK-CPT, a peptide-camptothecin conjugate, in colorectal cancer.
Fiche publication
Date publication
novembre 2022
Journal
Communications biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr GAIDDON Christian, Dr GROSS Isabelle
Tous les auteurs :
Hou L, Hou Y, Liang Y, Chen B, Zhang X, Wang Y, Zhou K, Zhong T, Long B, Pang W, Wang L, Han X, Li L, Xu C, Gross I, Gaiddon C, Fu W, Yao H, Meng X
Lien Pubmed
Résumé
To explore highly selective targeting molecules of colorectal cancer (CRC) is a challenge. We previously identified a twelve-amino acid peptide (LPKTVSSDMSLN, namely P-LPK) by phage display technique which may specifically binds to CRC cells. Here we show that P-LPK selectively bind to a panel of human CRC cell lines and CRC tissues. In vivo, Gallium-68 (Ga) labeled P-LPK exhibits selective accumulation at tumor sites. Then, we designed a peptide-conjugated drug comprising P-LPK and camptothecin (CPT) (namely P-LPK-CPT), and found P-LPK-CPT significantly inhibits tumor growth with fewer side effects in vitro and in vivo. Furthermore, through co-immunoprecipitation and molecular docking experiment, the glutamine transporter solute carrier 1 family member 5 (SLC1A5) was identified as the possible target of P-LPK. The binding ability of P-LPK and SLC1A5 is verified by surface plasmon resonance and immunofluorescence. Taken together, P-LPK-CPT is highly effective for CRC and deserves further development as a promising anti-tumor therapeutic for CRC, especially SLC1A5-high expression type.
Mots clés
Humans, Camptothecin, pharmacology, Molecular Docking Simulation, Peptides, metabolism, Glutamine, metabolism, Colorectal Neoplasms, drug therapy, Minor Histocompatibility Antigens, metabolism, Amino Acid Transport System ASC, metabolism
Référence
Commun Biol. 2022 11 14;5(1):1248