ArticleOncotarget2017
A bispecific enediyne-energized fusion protein targeting both epidermal growth factor receptor and insulin-like growth factor 1 receptor showing enhanced antitumor efficacy against non-small cell lung cancer.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
- Antitumor activity of a lectibody targeting cancer-associated high-mannose glycans.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Recombinant human epidermal growth factor combined with vacuum sealing drainage for wound healing in Bama pigs.Military Medical Research · 2021Article
- Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells.Journal of cellular biochemistry · 2021Article
- Enediyne-activated, EGFR-targeted human β-defensin 1 has therapeutic efficacy against non-small cell lung carcinoma.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Regulatory interactions between long noncoding RNA LINC00968 and miR-9-3p in non-small cell lung cancer: A bioinformatic analysis based on miRNA microarray, GEO and TCGA.Oncology letters · 2018Article
- Efficacy of combined treatment with vacuum sealing drainage and recombinant human epidermal growth factor for refractory wounds in the extremities and its effect on serum levels of IL-6, TNF-α and IL-2.Experimental and therapeutic medicine · 2018Article
- An arginine-rich cell penetrating peptide contained anti-gelatinase scFv-LDM fusion protein shows potent antitumor efficacy in pancreatic cancer.Journal of Cancer · 2018Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) both overexpressed on non-small cell lung cancer (NSCLC) and are known cooperatively to promote tumor progression and drug resistance. This study was to construct a novel bispecific fusion protein EGF-IGF-LDP-AE consisting of EGFR and IGF-IR specific ligands (EGF and IGF-1) and lidamycin, an enediyne antibiotic with potent antitumor activity, and investigate its antitumor efficacy against NSCLC. Binding and internalization assays showed that EGF-IGF-LDP protein could bind to NSCLC cells with high affinity and then internalized into cells with higher efficiency than that of monospecific proteins. In vitro, the enediyne-energized analogue of bispecific fusion protein (EGF-IGF-LDP-AE) displayed extremely potent cytotoxicity to NSCLC cell lines with IC50<10-11 mol/L. Moreover, the bispecific protein EGF-IGF-LDP-AE was more cytotoxic than monospecific proteins (EGF-LDP-AE and LDP-IGF-AE) and lidamycin. In vivo, EGF-IGF-LDP-AE markedly inhibited the growth of A549 xenografts, and the efficacy was more potent than that of lidamycin and monospecific counterparts. EGF-IGF-LDP-AE caused significant cell cycle arrest and it also induced cell apoptosis in a dosage-dependent manner. Pretreatment with EGF-IGF-LDP-AE inhibited EGF-, IGF-stimulated EGFR and IGF-1R phosphorylation, and blocked two main downstream signaling molecules AKT and ERK activation. These data suggested that EGF-LDP-IGF-AE protein would be a promising targeted agent for NSCLC patients with EGFR and/or IGF-1R overexpression.
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Registered trials
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