Flavonoid GL-V9 suppresses invasion and migration of human colorectal cancer cells by inhibiting PI3K/Akt and MMP-2/9 signaling.
Flavonoid GL-V9 suppresses invasion and migration of human colorectal cancer cells by inhibiting PI3K/Akt and MMP-2/9 signaling.
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DOI：
10.7150/jca.58710
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发表时间：
2021
影响因子：
3.9
通讯作者：
Huang H
中科院分区：
文献类型：
--
作者：
Gu Y;Yu J;Ding C;Zhou Y;Yang J;Yu W;Zhang X;Huang H
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化合物，具有抗肿瘤、抗炎等多种生物学功能。然而，GL-V9在CRC中的抗转移作用和相关机制仍然未知。在这项研究中，研究了GL-V9在CRC细胞中的抗侵袭和抗迁移活性。通过MTT法、细胞创伤愈合实验和transwell迁移实验，我们发现GL-V9以浓度依赖性方式抑制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）的蛋白表达水平以及活性均显著降低。进一步的机制分析显示GL-V9抑制MMP-2和MMP-9上游的PI 3 K/Akt信号通路。总之，我们的研究表明GL-V9可以通过PI 3 K/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结直肠癌转移的新药物。
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.