Abstract
EGb 761, the standard ginkgo biloba extract, is frequently prescribed in traditional Chinese medicine. Currently, there is no research focusing on its role in human colorectal cancer progression. In our study, we determined the anti-metastatic effect of EGb 761 on colorectal cancer cells and further explored the potential underlying regulatory mechanism. The cell migration and invasion assay indicated that EGb 761 treatment of colorectal cancer cells induced inhibition of cell migration and invasion ability in a concentration-dependent manner. To further explore the underlying regulatory mechanisms that may account for these findings, we performed quantitative real-time PCR (RT-qPCR), western blotting and immunoprecipitation analysis. The results showed that EGb 761 induced upregulation of LincRNA-p21 expression in a dose- and time-dependent manner. Overexpression of LincRNA-p21 also suppressed colorectal cancer cell metastasis. Furthermore, EGb 761 as well as LincRNA-p21 inhibited the expression of extracellular matrix protein, fibronectin. More importantly, RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays showed that LincRNA-p21 directly interacted with EZH2, and this interaction suppressed the expression of fibronectin. Finally, the gain and loss function assay revealed that EGb 761 inhibited migration, invasion and fibronctin expression by the LincRNA-p21/EZH2 pathway in colorectal cancer cells. Hence, EGb 761 may be a promising treatment regimen for colorectal cancer and restoration of LincRNA-p21 levels may be helpful for enhancing the anti-cancer effect of EGb 761.
Highlights
Colorectal cancer is associated with high mortality, and is one of the most general malignant cancers in digestive system [1]
We firstly evaluated the effect of EGb 761 on colorectal cancer cell metastasis
We investigated the effect of EGb 761 on colorectal cancer cell metastasis and further explored the underlying regulatory mechanism
Summary
Colorectal cancer is associated with high mortality, and is one of the most general malignant cancers in digestive system [1]. Revealing the underlying mechanism and finding new therapeutic approaches are necessary www.impactjournals.com/oncotarget for developing effective therapies for colorectal cancer patients. The extracts of ginkgo biloba are widely used for the supplements of sold herbal. The standard ginkgo biloba extract EGb 761, which contains 24% ginkgo lavone glycoside and 6% terpene lactones, is one the most important antioxidant properties [5]. Several studies have reported that the antioxidant activity of Ginkgo biloba extract could be helpful in the prevention and therapy of diseases and degenerative processes associated with oxidative stress [6,7,8]. The anti-tumor effect of EGb 761 on colorectal cancer is still not well known
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