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Tumor Biology

, Volume 37, Issue 5, pp 6881–6891 | Cite as

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

  • Jingjing Li
  • Yanwei Ye
  • Min Wang
  • Lisha Lu
  • Chao Han
  • Yubing Zhou
  • Jingmin Zhang
  • Zujiang Yu
  • Xiefu Zhang
  • Chunlin Zhao
  • Jianguo Wen
  • Quancheng Kan
Original Article

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

Gastric cancer FGFR4 PD173074 5-Fluorouracil In vivo 

Abbreviations

FGFR4

Fibroblast growth factor receptor 4

PD

PD173074

5-Fu

5-Fluorouracil

GC

Gastric cancer

NC

Negative control

Notes

Acknowledgments

This study was supported by Department of Gastrointestinal Surgery and Institute of Clinical Medicine, The First Affiliated Hospital, Zhengzhou University and National Natural Science Foundation of China, Grant No. 81201955. Furthermore, this work was supported by the Foundation of the First Affiliated Hospital of Zhengzhou University.

Conflicts of interest

None

Grant support

Support was granted by the National Natural Science Foundation of China (Grant No. 81201955) to Yanwei Ye.

Supplementary material

13277_2015_4411_MOESM1_ESM.doc (4.6 mb)
ESM 1 (DOC 4712 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Jingjing Li
    • 1
    • 2
  • Yanwei Ye
    • 2
    • 3
  • Min Wang
    • 4
  • Lisha Lu
    • 5
  • Chao Han
    • 6
  • Yubing Zhou
    • 6
  • Jingmin Zhang
    • 7
  • Zujiang Yu
    • 8
  • Xiefu Zhang
    • 2
    • 3
  • Chunlin Zhao
    • 2
    • 3
  • Jianguo Wen
    • 2
  • Quancheng Kan
    • 1
  1. 1.Department of GastroenterologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  2. 2.Institute of Clinical MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  3. 3.Department of Gastrointestinal SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  4. 4.Department of FunctionThe Fifth Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  5. 5.Department of OncologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  6. 6.Department of PharmacyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina
  7. 7.School of Pharmaceutical SciencesZhengzhou UniversityZhengzhouChina
  8. 8.Department of Infectious DiseasesThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

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