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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.


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Inhibitory effect of famitinib alone compared with 5-fluorouracil, cisplatin or paclitaxel alone on in BGC-823 xenografts. Growth curves of (A) xenografts and (B) animal weight treated with famitinib (50 mg/kg) or control (n=5 mice/group, mean ± SD). (C) H&E staining revealed areas of tissue necrosis following famitinib treatment (*) (magnification, ×200). (D) Tumor vascularization was significantly suppressed by famitinib according to CD34 expression (magnification, ×200). (E) Upon treatment, tumor xenografts were isolated and photographed. (F) Tumor volumes from each group were measured (n=5 mice/group, mean ± SD). CD, cluster of differentiation; 5-FU, 5-fluorouracil; DDP, cisplatin; PTX, paclitaxel; SD, standard deviation.
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f4-ol-0-0-4909: Inhibitory effect of famitinib alone compared with 5-fluorouracil, cisplatin or paclitaxel alone on in BGC-823 xenografts. Growth curves of (A) xenografts and (B) animal weight treated with famitinib (50 mg/kg) or control (n=5 mice/group, mean ± SD). (C) H&E staining revealed areas of tissue necrosis following famitinib treatment (*) (magnification, ×200). (D) Tumor vascularization was significantly suppressed by famitinib according to CD34 expression (magnification, ×200). (E) Upon treatment, tumor xenografts were isolated and photographed. (F) Tumor volumes from each group were measured (n=5 mice/group, mean ± SD). CD, cluster of differentiation; 5-FU, 5-fluorouracil; DDP, cisplatin; PTX, paclitaxel; SD, standard deviation.

Mentions: Mice were sacrificed 21 days after treatment, and tumors were isolated. Famitinib inhibited BGC-823 xenograft growth (tumor volume, 395.2 vs. 2,690.5 mm3, P<0.01; Fig. 4A), and animal weights were similar between groups (21.6 vs. 18.7 g, P=0.17; Fig. 4B).


Famitinib exerted powerful antitumor activity in human gastric cancer cells and xenografts
Inhibitory effect of famitinib alone compared with 5-fluorouracil, cisplatin or paclitaxel alone on in BGC-823 xenografts. Growth curves of (A) xenografts and (B) animal weight treated with famitinib (50 mg/kg) or control (n=5 mice/group, mean ± SD). (C) H&E staining revealed areas of tissue necrosis following famitinib treatment (*) (magnification, ×200). (D) Tumor vascularization was significantly suppressed by famitinib according to CD34 expression (magnification, ×200). (E) Upon treatment, tumor xenografts were isolated and photographed. (F) Tumor volumes from each group were measured (n=5 mice/group, mean ± SD). CD, cluster of differentiation; 5-FU, 5-fluorouracil; DDP, cisplatin; PTX, paclitaxel; SD, standard deviation.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4-ol-0-0-4909: Inhibitory effect of famitinib alone compared with 5-fluorouracil, cisplatin or paclitaxel alone on in BGC-823 xenografts. Growth curves of (A) xenografts and (B) animal weight treated with famitinib (50 mg/kg) or control (n=5 mice/group, mean ± SD). (C) H&E staining revealed areas of tissue necrosis following famitinib treatment (*) (magnification, ×200). (D) Tumor vascularization was significantly suppressed by famitinib according to CD34 expression (magnification, ×200). (E) Upon treatment, tumor xenografts were isolated and photographed. (F) Tumor volumes from each group were measured (n=5 mice/group, mean ± SD). CD, cluster of differentiation; 5-FU, 5-fluorouracil; DDP, cisplatin; PTX, paclitaxel; SD, standard deviation.
Mentions: Mice were sacrificed 21 days after treatment, and tumors were isolated. Famitinib inhibited BGC-823 xenograft growth (tumor volume, 395.2 vs. 2,690.5 mm3, P<0.01; Fig. 4A), and animal weights were similar between groups (21.6 vs. 18.7 g, P=0.17; Fig. 4B).

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