Background:
Breast cancer is one of the most common cancers worldwide among women, and angiogenesis has an important effect on its growth and metastasis. Glipizide, which is a widely used drug for type 2 diabetes mellitus, has been reported to inhibit tumor growth and metastasis by upregulating the expression of natriuretic peptide receptor A (NPRA). Atrial natriuretic peptide (ANP), the receptor of NPRA, plays an important role in angiogenesis. The purpose of this study was to explore the effect of glipizide combined with ANP on breast cancer growth and metastasis.
Methods:
To investigate the effect of glipizide combined with ANP on breast cancer, glipizide, ANP or glipizide combined with ANP was intraperitoneally injected into MMTV-PyMT mice. To explore whether the anticancer efficacy of glipizide combined with ANP was correlated with angiogenesis, a tube formation assay was performed.
Results:
Glipizide combined with ANP was found to inhibit breast cancer growth and metastasis in MMTV-PyMT mice, which spontaneously develop breast cancer. Furthermore, the inhibitory effect of ANP combined with glipizide was better than that of glipizide alone. ANP combined with glipizide significantly inhibited tube formation of human umbilical vein endothelial cells (HUVECs) by suppressing vascular endothelial growth factor (VEGF)/VEGFR2 (vascular endothelial growth factor receptor 2) signaling.
Conclusions:
These results demonstrate that glipizide combined with ANP has a greater potential than glipizide alone to be repurposed as effective agents for the treatment of breast cancer by targeting tumor-induced angiogenesis.
Our results show a positive correlation between TIMP-3 promoter methylation and gastric cancer risk and indicated that TIMP-3 promoter methylation may be used as a molecular marker for gastric cancer.
Both diabetes and breast cancer are common diseases worldwide, and diabetes is also linked to higher rates of breast cancer. Epidemiological data also indicate that diabetes may be one of the risk factors for breast cancer. However, the effect of diabetes on breast cancer progression in vivo is rarely reported. We established an ideal animal model of breast cancer using transgenic MMTV-PyMT mice, which spontaneously developed breast cancer. In this model, the animals copresented with diabetes mellitus, which allowed us to study the effect of high glucose on breast cancer. Compared with MMTV-PyMT mice without diabetes, MMTV-PyMT mice with diabetes developed heavier tumors and exhibited greater tumor volumes. Furthermore, high glucose promoted the invasiveness and metastasis of breast cancer in MMTV-PyMT mice. This breast cancer model in which mice copresented with diabetes provides a useful tool to study the effect of diabetes on breast cancer. Anat Rec, 302:269-277, 2019. Breast cancer is the most common malignancy in women worldwide and is one of the most common causes of cancer-related deaths in women. According to world health organization (WHO), global female breast cancer cases reached around 1.7 million in 2012, and accounted for 25% of the incidence of all female malignant tumors (Tao et al., 2015). Diabetes is a metabolic disorder that is characterized by elevating blood sugar levels and
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