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血小板衍生生长因子-D通过调节Notch1和基质金属蛋白酶-9促进结肠癌细胞的迁移、侵袭和增殖。

Platelet-derived growth factor-D promotes colorectal cancer cell migration, invasion and proliferation by regulating Notch1 and matrix metalloproteinase-9.

作者信息

Jiang Bin, Chen Jinhuang, Yuan Wenzheng, Ji Jintong, Liu Zhengyi, Wu Liang, Tang Qiang, Shu Xiaogang

机构信息

Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China.

出版信息

Oncol Lett. 2018 Feb;15(2):1573-1579. doi: 10.3892/ol.2017.7510. Epub 2017 Dec 5.

DOI:10.3892/ol.2017.7510
PMID:29434852
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5777126/
Abstract

Colorectal cancer (CRC) has been one of the most common types of cancer for decades worldwide. The pathogenesis of CRC is associated with the processes of activating oncogenes and inactivating anti-oncogenes. Platelet-derived growth factor-D (PDGF-D) was confirmed to regulate migration, invasion, proliferation, apoptosis and metastasis in various cancer cells. Overexpression of PDGF-D exists in a number of human malignancies, including pancreatic, prostate and breast cancer. However, the expression and function of PDGF-D and its associated molecular mechanism in CRC remain unclear. Thus, the expression of PDGF-D was detected in CRC tissues and human colon cancer lines. Subsequently, the effects of PDGF-D on the invasion, migration and proliferation of cancer cells were investigated. The corresponding molecular mechanism had also been explored. The present study revealed that PDGF-D was upregulated not only in CRC tissues but also in CRC cell lines, and simultaneously, facilitated the processes of migration, invasion and proliferation. Silencing PDGF-D in the SW480 cell line inhibited migration, invasion and proliferation distinctly, with reduced expression of Notch1 and matrix metalloproteinase-9. Furthermore, upregulating PDGF-D in HCT116 cells led to the opposite results. These findings indicate that PDGF-D may be developed into a potential therapeutic target for CRC treatment.

摘要

几十年来,结直肠癌(CRC)一直是全球最常见的癌症类型之一。CRC的发病机制与癌基因激活和抑癌基因失活过程相关。血小板衍生生长因子-D(PDGF-D)已被证实可调节多种癌细胞的迁移、侵袭、增殖、凋亡和转移。PDGF-D在包括胰腺癌、前列腺癌和乳腺癌在内的多种人类恶性肿瘤中均存在过表达。然而,PDGF-D在CRC中的表达、功能及其相关分子机制仍不清楚。因此,本研究检测了CRC组织和人结肠癌细胞系中PDGF-D的表达。随后,研究了PDGF-D对癌细胞侵袭、迁移和增殖的影响,并探索了相应的分子机制。本研究表明,PDGF-D不仅在CRC组织中上调,在CRC细胞系中也上调,同时促进了迁移、侵袭和增殖过程。在SW480细胞系中沉默PDGF-D可显著抑制迁移、侵袭和增殖,Notch1和基质金属蛋白酶-9的表达降低。此外,在HCT116细胞中上调PDGF-D则导致相反的结果。这些发现表明,PDGF-D可能成为CRC治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3f/5777126/7c876deeff0b/ol-15-02-1573-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3f/5777126/4cf25d6c934c/ol-15-02-1573-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3f/5777126/c670f572f4a4/ol-15-02-1573-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3f/5777126/86a5b5b076d3/ol-15-02-1573-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3f/5777126/7c876deeff0b/ol-15-02-1573-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3f/5777126/4cf25d6c934c/ol-15-02-1573-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3f/5777126/c670f572f4a4/ol-15-02-1573-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3f/5777126/86a5b5b076d3/ol-15-02-1573-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb3f/5777126/7c876deeff0b/ol-15-02-1573-g03.jpg

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