Title:Glipizide Combined with ANP Suppresses Breast Cancer Growth and Metastasis by Inhibiting Angiogenesis through VEGF/VEGFR2 Signaling
Volume: 22
Issue: 9
Author(s): Guanquan Mao, Shuting Zheng, Jinlian Li, Xiaohua Liu, Qin Zhou, Jinghua Cao, Qianqian Zhang, Lingyun Zheng, Lijing Wang*Cuiling Qi*
Affiliation:
- Institute of Basic Medical Sciences, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University,
Guangzhou, Guangdong 510006, China
- Institute of Basic Medical Sciences, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University,
Guangzhou, Guangdong 510006, China
- Guangdong Province Key Laboratory for Biotechnology Drug Candidates, School of Life
Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guang Zhou, Guangdong 510006, China
Keywords:
Glipizide, ANP, breast cancer, tumor growth, metastasis, tumor angiogenesis, HUVECs.
Abstract:
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: This study aimed at investigating 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.
Conclusion: These results demonstrate that glipizide combined with ANP has a greater potential than glipizide alone
to be repurposed as an effective agent for the treatment of breast cancer by targeting tumor-induced angiogenesis.