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VEGFA Involves in the Use of Fluvastatin and Zoledronate Against Breast Cancer

  • Original Article
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Pathology & Oncology Research

Abstract

Our study aimed to identify key genes involved in the use of fluvastatin and zoledronate against breast cancer, as well as to investigate the roles of vascular endothelial growth factor A (VEGFA) in the malignant behaviors of breast cancer cells. The expression data GSE33552 was downloaded from Gene Expression Omnibus database, including mocked-, fluvastatin- and zoledronate-treated MDA-MB-231 cells. Differentially expressed genes (DEGs) were identified in fluvastatin- and zoledronate-treated cells using limma package, respectively. Pathway enrichment analysis and protein-protein interaction (PPI) network analysis were then performed. Then we used shRNA specifically targeting VEGFA (shVEGFA) to knock down the expression of VEGFA in MDA-MB-231 cells. Cell viability assay, scratch wound healing assay, Transwell invasion assay and flow cytometry were performed to explore the effects of VEGFA knockdown on the malignant behaviors of breast cancer cells. VEGFA was up-regulated in both fluvastatin- and zoledronate-treated breast cancer cells. Moreover, VEGFA was a hub node in PPI network. In addition, VEGFA was successfully knocked down in MDA-MB-231 cells by shVEGFA. Suppression of VEGFA promoted the migration and invasion of breast cancer MDA-MB-231 cells. Suppression of VEGFA inhibited the apoptosis of MDA-MB-231 cells. Our results indicate that up-regulation of VEGFA may prevent the progression of breast cancer after fluvastatin and zoledronate treatment via inducing cell apoptosis and inhibiting migration and invasion. VEGFA may serve as a potential prognostic indicator for clinical outcome in the management of breast cancer.

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Authors and Affiliations

  1. Department of Medical Oncology, Harbin Medical University Cancer Hospital, Haping Road 150 of Nangang District, Harbin, Heilongjiang Province, 150086, China

    Haihong Pu, Qingyuan Zhang, Yan Wang, Jingxuan Wang & Minghui Zhang

  2. Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, 150086, Heilongjiang Province, China

    Chunbo Zhao

  3. Department of Radiation Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China

    Lei Shi

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  1. Haihong Pu
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  2. Qingyuan Zhang
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  3. Chunbo Zhao
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  4. Lei Shi
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  5. Yan Wang
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  6. Jingxuan Wang
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  7. Minghui Zhang
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Correspondence to Qingyuan Zhang.

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Pu, H., Zhang, Q., Zhao, C. et al. VEGFA Involves in the Use of Fluvastatin and Zoledronate Against Breast Cancer. Pathol. Oncol. Res. 24, 557–565 (2018). https://doi.org/10.1007/s12253-017-0277-4

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  • DOI: https://doi.org/10.1007/s12253-017-0277-4

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