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

Research Paper

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

Ye Gu1,2,3,4,5, Jiejie Yu2, Cong Ding1,2,3,4, Yifeng Zhou1,2,3,4, Jiangfeng Yang1,2,3,4, WeiPing Yu5, Xiaofeng Zhang1,2,3,4✉, Haitao Huang1,2,3,4✉

1. 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.
2. Department of Gastroenterology, The Fourth Clinical Medicine College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R.China.
3. Hangzhou Hospital & Institute of Digestive Diseases, Hangzhou, Zhejiang 310006, P.R.China.
4. Key Laboratory of Integrated Traditional Chinese and Western Medicine for Biliary and Pancreatic Diseases of Zhejiang Province, Hangzhou, Zhejiang 310006, P.R.China.
5. Department of Pathophysiology, Medical school of Southeast University, Nanjing, Jiangsu 210009, P.R. China.

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Gu Y, Yu J, Ding C, Zhou Y, Yang J, Yu W, Zhang X, Huang H. Flavonoid GL-V9 suppresses invasion and migration of human colorectal cancer cells by inhibiting PI3K/Akt and MMP-2/9 signaling. J Cancer 2021; 12(15):4542-4551. doi:10.7150/jca.58710. Available from https://www.jcancer.org/v12p4542.htm

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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.

Keywords: GL-V9, colorectal cancer, invasion, matrix metalloproteinases, PI3K/Akt