{'fraction_non_alphanumeric': 0.03546419697311949, 'fraction_numerical': 0.029591145245086967, 'mean_word_length': 5.90795631825273, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Screening a novel FGF 3 antagonist peptide with anti-tumor effects on breast cancer from a phage display library

Accumulating evidence has suggested that fibroblast growth factor 3 (FGF3) is expressed in breast cancer and correlates with the stage and grade of the disease. In the present study, a specific FGF3‐binding peptide (VLWLKNR, termed FP16) was isolated from a phage display heptapeptide library with FGF3. The peptide FP16 contained four identical (WLKN) amino acids and demonstrated high homology to the peptides of the 188‐194 (TMRWLKN) site of the high‐affinity FGF3 receptor fibroblast growth factor receptor 2. Functional analyses indicated that FP16 mediated significant inhibition of FGF3‐induced cell proliferation, arrested the cell cycle at the G0/G1 phase by increasing proliferation‐associated protein 2G4, suppressing cyclin D1 and proliferating cell nuclear antigen, and inhibited the FGF3‐induced activation of extracellular signal‐regulated kinase 1/2 and Akt kinase. Taken together, these results demonstrated that the peptide FP16, acting as an FGF3 antagonist, is a promising therapeutic agent for the treatment of breast cancer. Introduction Fibroblast growth factor 3 (FGF3), belonging to the family of fibroblast growth factors (FGFs), regulates several developmental processes, including brain patterning, branching morphogenesis and limb development, by binding, dimerizing and activating cell surface FGF receptors (FGFRs) (1). The extra‐cellular ligand‐binding portion of FGFRs is composed of three immunoglobulin‐like (Ig‐like) domains (D1‐D3). The crystal structure of the ectodomain of the FGFR complex with FGF demonstrated that the ligand‐binding domain of FGFR involves Ig‐like domains II and III (D2 and D3, respectively), as well as the linker between D2 and D3 (2). It has been reported that FGF3/FGFRs are associated with multiple biological activities, including cellular proliferation, differentiation, invasiveness and motility, thus demonstrating the potential to initiate and promote tumorigenesis (3). Breast cancer is one of the most common types of malignancy in females and the second most common cause of cancer‐associated mortality in females worldwide (4,5). The literature devoted to prognostic factors for breast cancer is extensive (6‐8). Histology, tumor stage and lymph‐node status are now supplemented with measurements of ploidy, steroid hormone receptors, S‐phase fractions, growth factors, oncogenes and oncogene products (9). Even though significant progress has been achieved in developing early diagnosis and treatment, acquired resistance to current chemotherapies and failure of endocrine‐targeted therapy in certain patients have resulted in a great clinical requirement for new therapeutic agents for breast cancer. The expression and associated amplification of FGF3 and FGFRs have been identified in breast cancer (10), and they correlate with advanced‐stage and high‐grade tumors, as well as decreased patient survival time (11). Therefore, it is likely that the development of antagonists targeting FGF3 and its receptors is a strategy that may assist in overcoming resistance to current chemotherapy and endocrine‐targeted therapy. In the present study, a high affinity FGF3‐binding peptide was isolated from a phage display library and the functions of the isolated peptide were Screening a novel FGF3 antagonist peptide with anti-tumor effects on breast cancer from a phage display library WEI WANG1*, TAO CHEN2*, HAICHENG LI2, YUHUI CHEN2, ZHILONG WU1, TONGMING FENG1, XILIN ZHANG1, QIU ZHONG2, QIANHONG ZHONG1, GUOZHOU LI3, LINA GUO4, LIN ZHOU2 and JIE ZHOU1 1Department of Clinical Laboratory and Disease Control, Foshan Fourth People's Hospital, Foshan, Guangdong 528000; 2Department of Provincial Reference Laboratory and Disease Control, Center for Tuberculosis Control of Guangdong, Guangzhou, Guangdong 510630; 3Department of Clinical Laboratory, Chronic Disease Control and Prevention Station of Dongguan, Dongguan, Guangdong 523008; 4Department of Nutrition, Guangdong Provincial Hospital of Chinese Traditional Medicine, Guangzhou, Guangdong 510120, P.R. China Received November 16, 2014; Accepted August 4, 2015 DOI: 10.3892/mmr.2015.4248 Correspondence to: Dr Lin Zhou, Department of Provincial Reference Laboratory and Disease Control, Center for Tuberculosis Control of Guangdong, 485 Huangpu Street, Guangzhou, Guangdong 510630,