Downregulation of PDGF-D Inhibits Proliferation and Invasion in Breast Cancer MDA-MB-231 Cells

Clinical Breast Cancer(2022)

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Abstract
This study demonstrated that silencing of PDGF-D could inhibit breast cancer cells proliferation, increase the apoptosis rate, and inhibit cell metastasis. These results suggested that PDGF-D gene may involve in the occurrence and development of breast cancer. Background: The platelet derived growth factor-D (PDGF-D) plays an important role in breast tumor aggressiveness. However, limited study has investigated the effect of silencing PDGF-D on the biological function of breast cancer. The purpose of this study is to clarify the potential value of PDGF-D as a target for breast cancer treatment. Methods: Reverse transcription-polymerase chain reaction and western blot were used to detect PDGF-D expression in 5 different breast cancer cells. The lentiviral vector was usd to silence PDGF-D in MDA-MB-231 cells. Then, Methyl Thiazolyl Tetrazolium was used to detect cell viability, 5-Ethynyl-2'- deoxyuridine and a soft agar assay were used to detect cell proliferation and clonality. Additionally, cell apoptosis after PDGF-D knockdown was measured by Annexin V/ Prodium Iodide staining, and cell migration was detected by trans-well assay. Survival rate and tumor size were measured by nude mice transplantation. Results: The MDA-MB-231 and SK-BR-3 cell lines showed higher PDGF-D expression than the MCF7 cell lines (P < .05). After the PDGF-D gene was silenced, the growth and colony forming abilitys ignificantly decreased (P < .05) together with the induction of apoptosis in MDA-MB-231 cells (P < .05). Moreover, MDA-MB-231 cells with PDGF-D silencing showed significantly diminished aggressive migration and invasion potential compared to other cells (P < .05). In vivo experiments also indicated that PDGF-D silencing inhibited tumor growth and improved the survival rate of tumor-bearing mice. Conclusion: Downregulation of PDGF-D had dramatic effects on breast cancer cell proliferation, apoptosis and migration, which indicates that it plays an important role in breast cancer development and progression. (C) 2021 Elsevier Inc. All rights reserved.
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Key words
Breast carcinoma,Migration,PDGF-D,Proliferation,Apoptosis
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