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Tumour Biol. 2016 May;37(5):6881-91. doi: 10.1007/s13277-015-4411-1. Epub 2015 Dec 11.

The over-expression of FGFR4 could influence the features of gastric cancer cells and inhibit the efficacy of PD173074 and 5-fluorouracil towards gastric cancer.

Li J1,2, Ye Y3,4, Wang M5, Lu L6, Han C7, Zhou Y7, Zhang J8, Yu Z9, Zhang X2,10, Zhao C2,10, Wen J2, Kan Q1.

Author information

1
Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
2
Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, 1 Jian-She Road, Zhengzhou, 450052, China.
3
Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, 1 Jian-She Road, Zhengzhou, 450052, China. yeyanwei1981@hotmail.com.
4
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, 1 Jian-She Road, Zhengzhou, 450052, China. yeyanwei1981@hotmail.com.
5
Department of Function, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
6
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
7
Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
8
School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
9
Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
10
Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, 1 Jian-She Road, Zhengzhou, 450052, China.

Abstract

The aim was to investigate the function of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the treatment value of agent targeted to FGFR4. Function assays in vitro and in vivo were performed to investigate the discrepancy of biological features among the GC cells with different expression of FGFR4. GC cells were treated with the single and combination of PD173074 (PD, an inhibitor of FGFR4) and 5-fluorouracil (5-Fu). The invasion ability were stronger, and the apoptosis rates were lower in MGC803 and BGC823 cells treated with FGFR4-LV5 (over-expression of FGFR4 protein) (P < 0.05). The proliferation ability of GC cells is reduced when treated by the single and combination of 5-Fu and PD while that of the FGFR4-LV5 group was less inhibited compared with control group (P < 0.05). The apoptosis rates are remarkably increased in GC cells treated with the single and combination of 5-Fu and PD (P < 0.05). However, the apoptosis rate obviously is reduced in GC cells treated with FGFR4-LV5 compared with control group (P < 0.05). The expression of PCNA and Bcl-XL is remarkably decreased, and the expression of Caspase-3 and cleaved Caspase-3 is obviously increased in GC cells treated with the single and combination of 5-Fu and PD. The tumor volumes of nude mice in FGFR4-LV5 group were much more increased (P < 0.05). The over-expression of FGFR4 enhanced the proliferation ability of GC in vitro and in vivo. The combination of 5-Fu and PD exerted synergetic effect in weakening the proliferation ability and promoting apoptosis in GC cells, while the over-expression of FGFR4 might inhibit the efficacy of two drugs.

KEYWORDS:

5-Fluorouracil; FGFR4; Gastric cancer; In vivo; PD173074

PMID:
26662569
DOI:
10.1007/s13277-015-4411-1
[Indexed for MEDLINE]

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