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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 triggered cell apoptosis. (A and B) Famitinib induced cell apoptosis in (A) BGC-823 and (B) MGC-803 cells compared with the control (n=3, mean ± standard deviation, **P<0.01), and downregulated B-cell lymphoma 2 in both cell lines. TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; DAPI, 4′,6-diamidino-2-phenylindole; BCL2, B-cell lymphoma 2.
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f3-ol-0-0-4909: Famitinib triggered cell apoptosis. (A and B) Famitinib induced cell apoptosis in (A) BGC-823 and (B) MGC-803 cells compared with the control (n=3, mean ± standard deviation, **P<0.01), and downregulated B-cell lymphoma 2 in both cell lines. TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; DAPI, 4′,6-diamidino-2-phenylindole; BCL2, B-cell lymphoma 2.

Mentions: Cell apoptosis is an important mechanism of cell growth inhibition (16); therefore, apoptosis was measured via TUNEL assay. Fig. 3 indicates that, compared with the control, famitinib increased apoptosis in BGC-823 and MGC-803 cell lines significantly (P<0.01), and downregulated BCL2.


Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts
Famitinib triggered cell apoptosis. (A and B) Famitinib induced cell apoptosis in (A) BGC-823 and (B) MGC-803 cells compared with the control (n=3, mean ± standard deviation, **P<0.01), and downregulated B-cell lymphoma 2 in both cell lines. TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; DAPI, 4′,6-diamidino-2-phenylindole; BCL2, B-cell lymphoma 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-ol-0-0-4909: Famitinib triggered cell apoptosis. (A and B) Famitinib induced cell apoptosis in (A) BGC-823 and (B) MGC-803 cells compared with the control (n=3, mean ± standard deviation, **P<0.01), and downregulated B-cell lymphoma 2 in both cell lines. TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; DAPI, 4′,6-diamidino-2-phenylindole; BCL2, B-cell lymphoma 2.
Mentions: Cell apoptosis is an important mechanism of cell growth inhibition (16); therefore, apoptosis was measured via TUNEL assay. Fig. 3 indicates that, compared with the control, famitinib increased apoptosis in BGC-823 and MGC-803 cell lines significantly (P<0.01), and downregulated BCL2.

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