title: Silencing of FGFR4 could influence the biological features of gastric cancer cells and its therapeutic value in gastric cancer.
abstract: To clarify the role of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the therapeutic value of BGJ398 targeted to FGFR4. We constructed lentivirus vectors to stably knockdown FGFR4 expression in GC cells. Function assays in vitro and in vivo, treated with 5-fluorouracil (5-Fu) and BGJ398, were performed to study the change of biological behaviors of GC cells and related mechanism. The proliferation and invasive ability of HGC27 and MKN45 significantly decreased while the apoptosis rate of GC cells obviously increased in shRNA group (P < 0.05). The expressions of Bcl-xl, FLIP, PCNA, vimentin, p-erk, and p-STAT3 significantly reduced while the expressions of caspase-3 and E-cadherin markly enhanced in shRNA group. The proliferation abilities of GC cells were more significantly inhibited by the combination of BGJ398 and 5-Fu in shRNA group (P < 0.05). Compared to negative control (NC), the single and combination of 5-Fu and BGJ398 all significantly increased the apoptosis rate of GC cells, especially in the combination group (P < 0.01). The single and combination of 5-Fu and BGJ398 decreased the expressions of PCNA, Bcl-xl, and FLIP while increased the expression of caspase-3 in GC cells, especially in shRNA groups. Furthermore, knockdown of FGFR4 expression might prevent the growth of GC in vivo. Silencing of FGFR4 expression could weaken the invasive ability, increase the apoptosis rate, and decrease the proliferation ability of GC cells in vitro and in vivo. Furthermore, the combination of 5-Fu and BGJ398 had synergy in inhibiting the proliferation ability and increasing apoptosis rate of GC cells, directing a new target drug in GC.
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. yeyanwei1981@hotmail.com.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. yeyanwei1981@hotmail.com.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Dongbao
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.|Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Function, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Xiefu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.|Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Chunlin
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Wen
authors.affiliation: Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.|Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: Quancheng
authors.initials: Q
authors.lastname: Kan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D015153:Blotting, Western; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D010671:Phenylurea Compounds / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D034622:RNA Interference; D000067492:RNAi Therapeutics / Q000379:methods; D051499:Receptor, Fibroblast Growth Factor, Type 4 / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D047368:Tumor Burden / Q000187:drug effects / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494811:BCL2L1 protein, human; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D010671:Phenylurea Compounds; D018809:Proliferating Cell Nuclear Antigen; D011743:Pyrimidines; D051020:bcl-X Protein; C568950:infigratinib; C496371:FGFR4 protein, human; D051499:Receptor, Fibroblast Growth Factor, Type 4; D053148:Caspase 3; D005472:Fluorouracil
keywords: 5-Fluorouracil; BGJ398; Fibroblast growth factor receptor 4; Gastric cancer; shRNA