title: RasGAP-derived peptide 38GAP potentiates the cytotoxicity of cisplatin through inhibitions of Akt, ERK and NF-κB in colon carcinoma HCT116 cells.
abstract: To increase the efficacy of currently used anti-cancer genotoxins, a combination use of different drugs is a potential new therapeutical tool. Here, we reported that a synthetic RasGAP-derived peptide 38GAP with RasGAP(301-326) and TAT penetration sequences could enhance the effect of chemotherapeutic agent CDDP in human colon carcinoma HCT116 cells. Our results showed that 38GAP significantly increased the CDDP-induced apoptosis in HCT116 cells. This synergistic effect was associated with abrogation of CDDP-induced G2/M arrest by down-regulations of phospho-Cdc2 and p21, and inhibitions of phospho-AKT, phospho-ERK and NF-κB. In animal models, 38GAP combined with CDDP significantly suppressed CT26 tumor growth, while 38GAP alone showed slight inhibitory effect. Our data suggest that 38GAP in combination with chemotherapeutics will become a potential therapeutic strategy for colon cancers.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Shenghua
authors.initials: S
authors.lastname: Zhang
authors.forename: Hongwei
authors.initials: H
authors.lastname: He
authors.forename: Wuli
authors.initials: W
authors.lastname: Zhao
authors.forename: Kaihuan
authors.initials: K
authors.lastname: Ren
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chen
authors.forename: Rong-guang
authors.initials: RG
authors.lastname: Shao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004249:DNA Damage; D015536:Down-Regulation / Q000187:drug effects; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D016328:NF-kappa B; D010446:Peptide Fragments; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002945:Cisplatin