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Attenuating tumour angiogenesis: a preventive role of metformin against breast cancer.

Gao S, Jiang J, Li P, Song H, Wang W, Li C, Kong D - Biomed Res Int (2015)

Bottom Line: No inhibition of breast tumour progression was detected.However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours.Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China.

ABSTRACT
Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed by in vivo assessment of metformin on tumour growth using xenograft breast cancer models. Significant inhibitory impact of metformin was observed in MCF-7, HeLa, and SKOV-3 cells, suggesting an antiproliferative property of metformin against breast, cervical, and ovarian tumour cells, respectively, with the breast tumour cells, MCF-7, being the most responsive. In vivo assessment was subsequently carried out, where mice with breast tumours were treated with metformin (20 mg/kg body weight) or sterile PBS solution for 15 consecutive days. No inhibition of breast tumour progression was detected. However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours. Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis.

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Effect of metformin treatment on tumour necrosis and angiogenesis. H&E staining of tumours obtained from Metformin and Control groups. Scale bar: 200 μm ((a), upper panels) and 100 μm ((a), lower panels). (b) Immunofluorescent staining of vWF (green) in tumours obtained from Metformin and Control groups. Scale bar: 100 μm. Nuclei were counter-stained with DAPI (blue). Area of tumour necrosis (c) and tumour blood vessel density (d) were quantified. Tumour necrosis was indicated by black arrows. Data are presented as means ± SD, n = 4-5. Images are representative of 4-5 animals from 3 separate experiments.
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fig3: Effect of metformin treatment on tumour necrosis and angiogenesis. H&E staining of tumours obtained from Metformin and Control groups. Scale bar: 200 μm ((a), upper panels) and 100 μm ((a), lower panels). (b) Immunofluorescent staining of vWF (green) in tumours obtained from Metformin and Control groups. Scale bar: 100 μm. Nuclei were counter-stained with DAPI (blue). Area of tumour necrosis (c) and tumour blood vessel density (d) were quantified. Tumour necrosis was indicated by black arrows. Data are presented as means ± SD, n = 4-5. Images are representative of 4-5 animals from 3 separate experiments.

Mentions: Despite the lack of inhibitory impact of metformin on tumour growth, subsequent histological analyses revealed marked increase of tumour necrosis in metformin-treated mice (143 ± 11% over control group, P < 0.01; Figures 3(a) and 3(c)). Furthermore, immunofluorescence staining of von Willebrand factor (vWF), a microvascular endothelial marker, also revealed reduced average blood vessel density in tumours obtained from the metformin-treated animals (69 ± 29% over control group, P < 0.02; Figures 3(b) and 3(d)), implicating an antiangiogenic impact of metformin.


Attenuating tumour angiogenesis: a preventive role of metformin against breast cancer.

Gao S, Jiang J, Li P, Song H, Wang W, Li C, Kong D - Biomed Res Int (2015)

Effect of metformin treatment on tumour necrosis and angiogenesis. H&E staining of tumours obtained from Metformin and Control groups. Scale bar: 200 μm ((a), upper panels) and 100 μm ((a), lower panels). (b) Immunofluorescent staining of vWF (green) in tumours obtained from Metformin and Control groups. Scale bar: 100 μm. Nuclei were counter-stained with DAPI (blue). Area of tumour necrosis (c) and tumour blood vessel density (d) were quantified. Tumour necrosis was indicated by black arrows. Data are presented as means ± SD, n = 4-5. Images are representative of 4-5 animals from 3 separate experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4389975&req=5

fig3: Effect of metformin treatment on tumour necrosis and angiogenesis. H&E staining of tumours obtained from Metformin and Control groups. Scale bar: 200 μm ((a), upper panels) and 100 μm ((a), lower panels). (b) Immunofluorescent staining of vWF (green) in tumours obtained from Metformin and Control groups. Scale bar: 100 μm. Nuclei were counter-stained with DAPI (blue). Area of tumour necrosis (c) and tumour blood vessel density (d) were quantified. Tumour necrosis was indicated by black arrows. Data are presented as means ± SD, n = 4-5. Images are representative of 4-5 animals from 3 separate experiments.
Mentions: Despite the lack of inhibitory impact of metformin on tumour growth, subsequent histological analyses revealed marked increase of tumour necrosis in metformin-treated mice (143 ± 11% over control group, P < 0.01; Figures 3(a) and 3(c)). Furthermore, immunofluorescence staining of von Willebrand factor (vWF), a microvascular endothelial marker, also revealed reduced average blood vessel density in tumours obtained from the metformin-treated animals (69 ± 29% over control group, P < 0.02; Figures 3(b) and 3(d)), implicating an antiangiogenic impact of metformin.

Bottom Line: No inhibition of breast tumour progression was detected.However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours.Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis.

View Article: PubMed Central - PubMed

Affiliation: Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin 300192, China.

ABSTRACT
Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed by in vivo assessment of metformin on tumour growth using xenograft breast cancer models. Significant inhibitory impact of metformin was observed in MCF-7, HeLa, and SKOV-3 cells, suggesting an antiproliferative property of metformin against breast, cervical, and ovarian tumour cells, respectively, with the breast tumour cells, MCF-7, being the most responsive. In vivo assessment was subsequently carried out, where mice with breast tumours were treated with metformin (20 mg/kg body weight) or sterile PBS solution for 15 consecutive days. No inhibition of breast tumour progression was detected. However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours. Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis.

Show MeSH
Related in: MedlinePlus