PURPOSE: This study aims to investigate the role of siRNA silencing fibroblast growth factor receptor (FGFR) expression in promoting chemotherapy effect of gastric cancer and to explore its mechanism. METHODS: Human gastric cancer cells MGC80-3 were divided into four groups: control group, cisplatin group (2 μg/L), cisplatin (2 μg/L) + siRNA group and siRNA group. The expressions of FGFR in four groups were detected by immunofluorescence. The cell proliferation and apoptosis were detected by MTT assay and flow cytometry. The protein expression levels of vascular endothelial growth factor receptor (VEGFR), caspase-3 and Bax were detected by Western blot. Further, animal model of gastric cancer was established and divided into four groups as in vitro experiment. The expression of FGFR mRNA in tumor tissue was detected by the real-time fluorescence quantitative polymerase chain reaction. The size of tumor was measured to analyze the effects of treatment. Histopathological detections were performed by hematoxylin and eosin staining and immunohistochemistry. RESULTS: For in vitro experiment, significant decrease inFGFR expression, inhibition of proliferation and promotion of apoptosis were observed in siRNA-treated cells, so as cisplatin group. siRNA also resulted in the reduction of VEGFR and rise in apoptosis-related protein (caspase-3). As for the experiment in vivo, siRNA also suppressed the expression of FGFR and enhanced tumor shrink. Furthermore, the co-administration of siRNA and cisplatin revealed a more excellent antitumor effect than other therapies. CONCLUSIONS: siRNA can effectively suppress FGFR expression and cell proliferation, but promote apoptosis in vitro and also inhibit tumor growth and FGFR production in vivo. siRNA-participated chemotherapy may provide an efficient therapeutic approach to treat gastric cancer.
PURPOSE: This study aims to investigate the role of siRNA silencing fibroblast growth factor receptor (FGFR) expression in promoting chemotherapy effect of gastric cancer and to explore its mechanism. METHODS:Humangastric cancer cells MGC80-3 were divided into four groups: control group, cisplatin group (2 μg/L), cisplatin (2 μg/L) + siRNA group and siRNA group. The expressions of FGFR in four groups were detected by immunofluorescence. The cell proliferation and apoptosis were detected by MTT assay and flow cytometry. The protein expression levels of vascular endothelial growth factor receptor (VEGFR), caspase-3 and Bax were detected by Western blot. Further, animal model of gastric cancer was established and divided into four groups as in vitro experiment. The expression of FGFR mRNA in tumor tissue was detected by the real-time fluorescence quantitative polymerase chain reaction. The size of tumor was measured to analyze the effects of treatment. Histopathological detections were performed by hematoxylin and eosin staining and immunohistochemistry. RESULTS: For in vitro experiment, significant decrease inFGFR expression, inhibition of proliferation and promotion of apoptosis were observed in siRNA-treated cells, so as cisplatin group. siRNA also resulted in the reduction of VEGFR and rise in apoptosis-related protein (caspase-3). As for the experiment in vivo, siRNA also suppressed the expression of FGFR and enhanced tumor shrink. Furthermore, the co-administration of siRNA and cisplatin revealed a more excellent antitumor effect than other therapies. CONCLUSIONS: siRNA can effectively suppress FGFR expression and cell proliferation, but promote apoptosis in vitro and also inhibit tumor growth and FGFR production in vivo. siRNA-participated chemotherapy may provide an efficient therapeutic approach to treat gastric cancer.
Authors: W Eberhardt; H Wilke; G Stamatis; M Stuschke; A Harstrick; H Menker; B Krause; M R Müeller; M Stahl; M Flasshove; V Budach; D Greschuchna; N Konietzko; H Sack; S Seeber Journal: J Clin Oncol Date: 1998-02 Impact factor: 44.544
Authors: C Herold-Mende; H H Steiner; T Andl; D Riede; A Buttler; C Reisser; N E Fusenig; M M Mueller Journal: Lab Invest Date: 1999-12 Impact factor: 5.662
Authors: W A Peters; P Y Liu; R J Barrett; R J Stock; B J Monk; J S Berek; L Souhami; P Grigsby; W Gordon; D S Alberts Journal: J Clin Oncol Date: 2000-04 Impact factor: 44.544