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类黄酮GL-V9通过抑制PI3K/Akt和MMP-2/9信号通路来抑制人结肠癌细胞的侵袭和迁移。

Flavonoid GL-V9 suppresses invasion and migration of human colorectal cancer cells by inhibiting PI3K/Akt and MMP-2/9 signaling.

作者信息

Gu Ye, Yu Jiejie, Ding Cong, Zhou Yifeng, Yang Jiangfeng, Yu WeiPing, Zhang Xiaofeng, Huang Haitao

机构信息

Department of Gastroenterology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310006, P.R.China.

Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R.China.

出版信息

J Cancer. 2021 Jun 1;12(15):4542-4551. doi: 10.7150/jca.58710. eCollection 2021.

Abstract

Tumor distant metastasis is the primary cause of death in colorectal cancer (CRC) patients. GL-V9 is a newly synthesized flavonoid derivative with several beneficial biological functions including anti-tumor and anti-inflammation. However, the anti-metastatic effect of GL-V9 and related mechanisms in CRC remains unknown. In this study, the anti-invasive and anti-migratory activities of GL-V9 were investigated in CRC cells. Using MTT assay, cell wound healing assay, and transwell migration assay, we showed that GL-V9 suppressed CRC cell viability, migration, and invasion in a concentration-dependent manner. In addition, the protein expression levels as well as activities of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) were significantly reduced after GL-V9 treatment. Further analysis of the underlying mechanism revealed that GL-V9 inhibited PI3K/Akt signaling pathway upstream of MMP-2 and MMP-9. In conclusion, our study demonstrated that GL-V9 could suppress CRC cell invasion and migration through PI3K/Ak and MMP-2/9 axis. Therefore, GL-V9 might be a potential novel therapeutic agent against CRC metastasis.

摘要

肿瘤远处转移是结直肠癌(CRC)患者死亡的主要原因。GL-V9是一种新合成的黄酮类衍生物,具有多种有益的生物学功能,包括抗肿瘤和抗炎作用。然而,GL-V9在CRC中的抗转移作用及其相关机制尚不清楚。在本研究中,我们研究了GL-V9在CRC细胞中的抗侵袭和抗迁移活性。通过MTT法、细胞划痕愈合试验和Transwell迁移试验,我们发现GL-V9以浓度依赖的方式抑制CRC细胞的活力、迁移和侵袭。此外,GL-V9处理后,基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的蛋白表达水平及活性显著降低。对潜在机制的进一步分析表明,GL-V9抑制了MMP-2和MMP-9上游的PI3K/Akt信号通路。总之,我们的研究表明GL-V9可通过PI3K/Ak和MMP-2/9轴抑制CRC细胞的侵袭和迁移。因此,GL-V9可能是一种潜在的抗CRC转移的新型治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11ea/8210567/311958fe12eb/jcav12p4542g001.jpg

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