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Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts

View Article: PubMed Central - PubMed

ABSTRACT

Famitinib (SHR1020), a novel multi-targeted tyrosine kinase inhibitor, has antitumor activity against several solid tumors via targeting vascular endothelial growth factor receptor 2, c-Kit and platelet-derived growth factor receptor β. The present study investigated famitinib's activity against human gastric cancer cells in vitro and in vivo. Cell viability and apoptosis were measured, and cell cycle analysis was performed following famitinib treatment using 3-(4,5-dimethylthiazol −2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and western blotting. Subsequently, cluster of differentiation 34 staining was used to evaluate microvessel density. BGC-823-derived xenografts in nude mice were established to assess drug efficacy in vivo. Famitinib inhibited cell proliferation by inducing cell cycle arrest at the G2/M phase and caused cell apoptosis in a dose-dependent manner in gastric cancer cell lines. In BGC-823 xenograft models, famitinib significantly slowed tumor growth in vivo via inhibition of angiogenesis. Compared with other chemotherapeutics such as 5-fluorouracil, cisplatin or paclitaxel alone, famitinib exhibited the greatest tumor suppression effect (>85% inhibition). The present study demonstrated for the first time that famitinib has efficacy against human gastric cancer in vitro and in vivo, which may lay the foundations for future clinical trials.

No MeSH data available.


Related in: MedlinePlus

Famitinib induced cell cycle arrest at the G2/M phase. (A and B) Cell cycle was arrested in cell lines BGC-823 and MGC-803 (n=3; mean ± SD; *P<0.05). (C) With famitinib treatment, cyclin B1 was upregulated in both cell lines according to western blot analysis. SD, standard deviation; PI, propidium iodide.
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f2-ol-0-0-4909: Famitinib induced cell cycle arrest at the G2/M phase. (A and B) Cell cycle was arrested in cell lines BGC-823 and MGC-803 (n=3; mean ± SD; *P<0.05). (C) With famitinib treatment, cyclin B1 was upregulated in both cell lines according to western blot analysis. SD, standard deviation; PI, propidium iodide.

Mentions: The cell cycle was next analyzed following famitinib treatment, and it was observed that the number of G2/M-phase cells increased in BGC-823 (27.98 vs. 14.25%) and MGC-803 (58.23 vs. 10.72%) cells compared with the control (P=0.04 and P=0.02, respectively; Fig. 2A and B). Cell cycle arrest at the G2/M phase was confirmed by increased expression of the cell metaphase-specific protein cyclin B1 (Fig. 2C).


Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts
Famitinib induced cell cycle arrest at the G2/M phase. (A and B) Cell cycle was arrested in cell lines BGC-823 and MGC-803 (n=3; mean ± SD; *P<0.05). (C) With famitinib treatment, cyclin B1 was upregulated in both cell lines according to western blot analysis. SD, standard deviation; PI, propidium iodide.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998225&req=5

f2-ol-0-0-4909: Famitinib induced cell cycle arrest at the G2/M phase. (A and B) Cell cycle was arrested in cell lines BGC-823 and MGC-803 (n=3; mean ± SD; *P<0.05). (C) With famitinib treatment, cyclin B1 was upregulated in both cell lines according to western blot analysis. SD, standard deviation; PI, propidium iodide.
Mentions: The cell cycle was next analyzed following famitinib treatment, and it was observed that the number of G2/M-phase cells increased in BGC-823 (27.98 vs. 14.25%) and MGC-803 (58.23 vs. 10.72%) cells compared with the control (P=0.04 and P=0.02, respectively; Fig. 2A and B). Cell cycle arrest at the G2/M phase was confirmed by increased expression of the cell metaphase-specific protein cyclin B1 (Fig. 2C).

View Article: PubMed Central - PubMed

ABSTRACT

Famitinib (SHR1020), a novel multi-targeted tyrosine kinase inhibitor, has antitumor activity against several solid tumors via targeting vascular endothelial growth factor receptor 2, c-Kit and platelet-derived growth factor receptor &beta;. The present study investigated famitinib's activity against human gastric cancer cells in vitro and in vivo. Cell viability and apoptosis were measured, and cell cycle analysis was performed following famitinib treatment using 3-(4,5-dimethylthiazol &minus;2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick end labeling assay and western blotting. Subsequently, cluster of differentiation 34 staining was used to evaluate microvessel density. BGC-823-derived xenografts in nude mice were established to assess drug efficacy in vivo. Famitinib inhibited cell proliferation by inducing cell cycle arrest at the G2/M phase and caused cell apoptosis in a dose-dependent manner in gastric cancer cell lines. In BGC-823 xenograft models, famitinib significantly slowed tumor growth in vivo via inhibition of angiogenesis. Compared with other chemotherapeutics such as 5-fluorouracil, cisplatin or paclitaxel alone, famitinib exhibited the greatest tumor suppression effect (&gt;85% inhibition). The present study demonstrated for the first time that famitinib has efficacy against human gastric cancer in vitro and in vivo, which may lay the foundations for future clinical trials.

No MeSH data available.


Related in: MedlinePlus