Attenuating Tumour Angiogenesis: A Preventive Role of Metformin against Breast Cancer

Gao, Shan; Jiang, Jingcheng; Li, Panpan; Song, Huijuan; Wang, Weiwei; Li, Chen

doi:10.1155/2015/592523

Cited by 10 publications

(10 citation statements)

References 15 publications

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“…The findings that metformin blocked vascular invasion of thyroid tumors of Thrb PV/PV Pten +/− mice are in line with the reports in which the anti-angiogenic effects of metformin were described in colon cancer [39], HER2+ tumor cells [40] and breast tumors [41, 42]. In colon cancer, metformin was shown to down regulate tumor angiogenesis and augment the antitumor effect oxaliplatin [39].…”

Section: Discussionsupporting

confidence: 87%

“…In HER2+ tumor cells, metformin treatment decreased microvessel-induced inhibition of tumor angiogenesis [40]. In breast tumors, metformin reduced tumor microvessel density and attenuated tumor angiogenesis [41, 42]. While metformin was shown to have anti-neoplastic effects in diabetic patients with differentiated thyroid cancer [25], whether metformin has anti-angiogenic effects in thyroid cancer progression remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

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Metformin blocks progression of obesity-activated thyroid cancer in a mouse model

et al. 2016

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Compelling epidemiologic evidence indicates that obesity is associated with a high risk of human malignancies, including thyroid cancer. We previously demonstrated that a high fat diet (HFD) effectively induces the obese phenotype in a mouse model of aggressive follicular thyroid cancer (ThrbPV/PVPten+/−mice). We showed that HFD promotes cancer progression through aberrant activation of the leptin-JAK2-STAT3 signaling pathway. HFD-promoted thyroid cancer progression allowed us to test other molecular targets for therapeutic opportunity for obesity-induced thyroid cancer. Metformin is a widely used drug to treat patients with type II diabetes. It has been shown to reduce incidences of neoplastic diseases and cancer mortality in type II diabetes patients. The present study aimed to test whether metformin could be a therapeutic for obesity-activated thyroid cancer. ThrbPV/PVPten+/−mice were fed HFD together with metformin or vehicle-only, as controls, for 20 weeks. While HFD-ThrbPV/PVPten+/−mice had shorter survival than LFD-treated mice, metformin had no effects on the survival of HFD-ThrbPV/PVPten+/−mice. Remarkably, metformin markedly decreased occurrence of capsular invasion and completely blocked vascular invasion and anaplasia in HFD-ThrbPV/PVPten+/−mice without affecting thyroid tumor growth. The impeded cancer progression was due to the inhibitory effect of metformin on STAT3-ERK-vimentin and fibronectin-integrin signaling to decrease tumor cell invasion and de-differentiation. The present studies provide additional molecular evidence to support the link between obesity and thyroid cancer risk. Importantly, our findings suggest that metformin could be used as an adjuvant in combination with antiproliferative modalities to improve the outcome of patients with obesity-activated thyroid cancer.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

Metformin blocks progression of obesity-activated thyroid cancer in a mouse model

et al. 2016

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“…8 Interestingly, another study has indicated that administration of 0.1 mM metformin for 24 hours is able to supress 50% of HeLa cell growth. 23 An inhibitory effect of metformin is also observed in some thyroid cancer cell lines, which incubated with various doses of metformin for 24-72 hours. 18 During 24 hour incubation, a higher dose of metformin (≥40 mM) was required for inhibition of cell proliferation of thyroid cancer cell lines.…”

Section: Discussionmentioning

confidence: 95%

Metformin Enhances Anti-proliferative Effect of Cisplatin in Cervical Cancer Cell Line

Yudhani

Pesik

Indarto

2016

Indones J Clin Pharm

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Cervival cancer is one of the top rank of gynecological malignancy in the world, leading to high morbidity and mortality rates. Cisplatin is a chemotherapeutic agent that is generally used to treat cervical cancer but the use of this drug is limited because of serious side effects. Metformin, a diabetic drug, decreases not only blood glucose levels but also cell viability of some cancer cells. The aim of this study was to investigate the anti-proliferative effect of combination metformin and cisplatin in HeLa cells (cervical cancer cell line). Anti-proliferative effect of these combined drugs was analized using MTT assay, combination index assay and HeLa cell morphology. Inhibitory concentration (IC 50) of cisplatin and metformin was determined before performing combination index assay. Administration of 10 mM metformin showed inhibition of HeLa cell proliferation and it reached 50% inhibition of cell proliferation at 60 mM. Whilst, cisplatin showed a stronger anti-proliferative effect with initial inhibition dose at 12 µM and IC 50 dose at 44 µM. Combination of 30 mM metformin and 5 µM cisplatin indicated the strongest anti-proliferative effect on HeLa cell. In conclusion, metformin may become a promising drug for treatment of cervical cancer in future which enhances anti-proliferative effect of cisplatin.

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“…In detail, this study found that the metformin inhibited solid tumors in the normal mice by increasing the number of CD8 + tumor-infiltrating lymphocytes. In addition, the metformin also could reduce insulin resistance and attenuate tumor angiogenesis [30][31][32]. By elucidating the mechanisms that are involved in the anticancer effect of metformin, could be benefit for performing better therapeutic strategies, improve the prognosis of patients with T2D and cancer.…”

Section: Discussionmentioning

confidence: 99%

Metformin use improves the survival of diabetic combined small-cell lung cancer patients

et al. 2015

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Metformin has been reported having potential anticancer effect on kinds of solid tumors, but its role in combined small-cell lung cancer (C-SCLC) remains indistinct. This study aimed to explore whether metformin use has a prognosis benefit in diabetic C-SCLC patients. A total of 259 C-SCLC patients with diabetes were enrolled in our study. The clinicopathological parameters and survival data were collected and analyzed. The correlation between metformin use and clinicopathological characters was analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of metformin use for C-SCLC. The metformin was used in 120 (46.3 %) patients. Our data showed that the metformin use decreased C-SCLC recurrence rate (p = 0.001). The median overall survival (OS) and disease-free survival (DFS) were significantly better in the metformin use group compared to non-metformin group (OS 19.0 vs 11.5 months, p < 0.001; DFS 10.5 vs 7.0 months, p < 0.001). Multivariate analyses indicated that metformin use was an independent prognostic factor for OS and DFS (p = 0.001 vs p = 0.018). The metformin use improved the long-term outcome of C-SCLC patients with diabetes, which might be considered a potential useful prognostic indicator and anticancer drug.

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Attenuating Tumour Angiogenesis: A Preventive Role of Metformin against Breast Cancer

Cited by 10 publications

References 15 publications

Metformin blocks progression of obesity-activated thyroid cancer in a mouse model

Metformin blocks progression of obesity-activated thyroid cancer in a mouse model

Metformin Enhances Anti-proliferative Effect of Cisplatin in Cervical Cancer Cell Line

Metformin use improves the survival of diabetic combined small-cell lung cancer patients

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