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Silencing of FGFR4 could influence the biological features of gastric cancer cells and its therapeutic value in gastric cancer

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Tumor Biology

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.

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Abbreviations

FGFR4:

Fibroblast growth factor receptor 4

5-Fu:

5-Fluorouracil

GC:

Gastric cancer

NC:

Negative control

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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.

Conflicts of interest

None

Grant support

Natural Science Foundation of China (Grant No. 81201955) to Yanwei Ye

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Author notes

    Authors and Affiliations

    1. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

      Yanwei Ye, Dongbao Jiang, **efu Zhang & Chunlin Zhao

    2. Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

      Yanwei Ye, Dongbao Jiang, **g**g Li, **efu Zhang, Chunlin Zhao, Jianguo Wen & Quancheng Kan

    3. Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

      **g**g Li & Quancheng Kan

    4. Department of Function, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, China

      Min Wang

    5. Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

      Chao Han

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    1. Yanwei Ye
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    Correspondence to Yanwei Ye.

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    Yanwei Ye and Dongbao Jiang contributed equally to this work.

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    Ye, Y., Jiang, D., Li, J. et al. Silencing of FGFR4 could influence the biological features of gastric cancer cells and its therapeutic value in gastric cancer. Tumor Biol. 37, 3185–3195 (2016). https://doi.org/10.1007/s13277-015-4100-0

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