Zhang Kun, Tian Ruoxi, Wang Guanglin, Zhang Jianfeng, Ma Hongqin, Hu Xuhua, Xi Jinchuan, Wang Guiying
General Surgical Department, The Third Hospital of Hebei Medical University, Shijiazhuang, People's Republic of China.
Basic Medical College, Tianjin Medical University, Tianjin, People's Republic of China.
Onco Targets Ther. 2020 Aug 21;13:8373-8382. doi: 10.2147/OTT.S248085. eCollection 2020.
A disintegrin and metallopeptidase with thrombospondin motifs (ADAMTSs), whose expression is dysregulated in various cancers, is implicated in cancer development. Herein, we aimed to investigate the functional role of ADAMTS8 in breast cancer (BC) and explore the underlying mechanisms.
The protein expression of ADAMTS8 in BC cell lines and tumor tissues from BC patients was quantified by Western blot. ADAMTS8 overexpression was induced by transfection with pEZ-M90-ADAMTS8 plasmid using lipofectamine 2000. To generate ADAMTS8 stable knockdown cells, MDA-MB-231 cells were transfected with psi-H1-ADAMTS8siRNA plasmids. Cell counting kit-8 (CCK-8) assay, wound-healing assay, transwell assay and flow cytometry assay were employed to analyze the effects of ADAMTS8 on the proliferation, migration, invasion and apoptosis of BC cells. Chemosensitivity also was assessed using CCK-8 assay. The expressions of β-catenin, MMP-7 and c-Myc were measured by Western blot.
Our results showed that ADAMTS8 expression was significantly lower in BC tissues than that in adjacent non-tumor tissues. Overexpression of ADAMTS8 in MDA-MB-453 cells could inhibit the cell proliferation, migration and invasion and promote apoptosis. ADAMTS8 knockdown displayed the reverse effect in MDA-MB-231 cells. Consistently, in vivo data showed that ADAMTS8 overexpression led to a reduction in tumor growth. In addition, chemosensitivity testing in MDA-MB-453 cells transfected with pEZ-M90-ADAMTS8 plasmid indicated that cisplatin inhibited cell growth dramatically. Furthermore, attenuated β-catenin, MMP-7 and c-Myc level was detected after ADAMTS8 overexpression.
These results indicate that increased ADAMTS8 expression could modify the progression of BC by inhibiting cell proliferation and invasion while promoting the apoptosis of BC cells. Thus, ADAMTS8 represents a potential therapeutic target for BC therapy.
含血小板反应蛋白基序的解聚素和金属蛋白酶（ADAMTSs）在多种癌症中表达失调，与癌症发展有关。在此，我们旨在研究ADAMTS8在乳腺癌（BC）中的功能作用，并探索其潜在机制。
通过蛋白质印迹法定量分析BC细胞系和BC患者肿瘤组织中ADAMTS8的蛋白表达。使用脂质体2000通过转染pEZ-M90-ADAMTS8质粒诱导ADAMTS8过表达。为了生成ADAMTS8稳定敲低细胞，用psi-H1-ADAMTS8siRNA质粒转染MDA-MB-231细胞。采用细胞计数试剂盒-8（CCK-8）检测、伤口愈合检测、Transwell检测和流式细胞术检测分析ADAMTS8对BC细胞增殖、迁移、侵袭和凋亡的影响。还用CCK-8检测评估化疗敏感性。通过蛋白质印迹法检测β-连环蛋白、基质金属蛋白酶-7（MMP-7）和c-Myc的表达。
我们的结果表明，BC组织中ADAMTS8的表达明显低于相邻的非肿瘤组织。MDA-MB-453细胞中ADAMTS8的过表达可抑制细胞增殖、迁移和侵袭，并促进凋亡。ADAMTS8敲低在MDA-MB-231细胞中表现出相反的作用。同样，体内数据表明ADAMTS8过表达导致肿瘤生长减少。此外，对用pEZ-M90-ADAMTS8质粒转染的MDA-MB-453细胞进行的化疗敏感性测试表明，顺铂显著抑制细胞生长。此外，ADAMTS8过表达后检测到β-连环蛋白、MMP-7和c-Myc水平降低。
这些结果表明，ADAMTS8表达增加可通过抑制细胞增殖和侵袭，同时促进BC细胞凋亡来改变BC的进展。因此，ADAMTS8是BC治疗的一个潜在治疗靶点。
