title: Tumor-penetrating peptide fused to a pro-apoptotic peptide facilitates effective gastric cancer therapy.
abstract: KLA (sequence, KLAKLAKKLAKLAK) is a peptide which leads to programmed cell death by disrupting the mitochondrial membrane. However, low penetration in tumors greatly limits its application and efficacy. To develop a KLA-based cancer therapy, KLA-iRGD, a recombinant protein was constructed. It consists of the KLA peptide and iRGD (CRGDKGPDC), a tumor-homing peptide with high penetration into tumor tissue and cells. The conjugated KLA exhibits pro-apoptotic activity to prevent the growth of a tumor once it is inside the cell. Once KLA-iRGD is internalized in cultured tumor cells, via the activation of the receptor neuropilin-1, it spreads extensively throughout the mass of the tumor. The recombinant KLA-iRGD protein showed antitumor activity in vivo in mice and in vitro in tumor cell lines. Repeated treatment with KLA-iRGD greatly prevented tumor growth, resulting in a considerable reduction in tumor volume. According to our data, KLA-iRGD may serve as a potential anticancer agent with limited systemic toxicity and high selectivity for the treatment of MKN45 gastric cancer, which may lead to the enhancement of new targeted anticancer agents.
authors.affiliation: The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, P.R. China.
authors.forename: Xihan
authors.initials: X
authors.lastname: Li
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, P.R. China.
authors.forename: Huizi
authors.initials: H
authors.lastname: Sha
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, P.R. China.
authors.forename: Lianru
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University, Nanjing, Jiangsu, P.R. China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Bian
authors.affiliation: Key Laboratory of Human Functional Genomics of Jiangsu Province, Jiangsu Diabetes Center, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: The Comprehensive Cancer Centre, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D051336:Mitochondrial Membranes / Q000378:metabolism; D009842:Oligopeptides / Q000235:genetics* / Q000627:therapeutic use; D010455:Peptides / Q000235:genetics* / Q000627:therapeutic use; D011993:Recombinant Fusion Proteins / Q000235:genetics* / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000235:genetics* / Q000628:therapy; D023041:Xenograft Model Antitumor Assays
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C535058:KLA peptide; C569656:N-end cysteine peptide tumor-homing peptide; D009842:Oligopeptides; D010455:Peptides; D011993:Recombinant Fusion Proteins