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.

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.

• Authors: Jingjing Li, Yanwei Ye, Min Wang, Lisha Lu, Chao Han, Yubing Zhou, Jingmin Zhang, Zujiang Yu, Xiefu Zhang, Chunlin Zhao, Jianguo Wen, Quancheng Kan
• Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine (Tumour Biol) Vol. 37 Issue 5 Pg. 6881-91 (May 2016) ISSN: 1423-0380 [Electronic] Netherlands
• PMID: 26662569 (Publication Type: Journal Article)

Chemical References

• PD 173074
• Pyrimidines
• Receptor, Fibroblast Growth Factor, Type 4
• Fluorouracil

Topics

• Animals
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Disease Models, Animal
• Fluorouracil (pharmacology)
• Gene Expression
• Humans
• Male
• Mice
• Pyrimidines (pharmacology)
• Receptor, Fibroblast Growth Factor, Type 4 (genetics)
• Stomach Neoplasms (genetics, pathology)
• Xenograft Model Antitumor Assays