Ginkgo biloba extract EGb 761–induced upregulation of LincRNA-p21 inhibits colorectal cancer metastasis by associating with EZH2
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Tingting Liu1,2, Junzhong Zhang2, Zhongqiu Chai3, Gang Wang4, Naiqiang Cui1 and Bing Zhou1
1Department of Integrated Chinese and Western Medicine Surgery, Tianjin University of Traditional Chinese Medicine, Tianjin, China
2Department of Anorectal Surgery, Tianjin Binhai New Area Traditional Chinese Medicine Hospital, Tianjin, China
3Department of Science and Education, Tianjin Binhai New Area Traditional Chinese Medicine Hospital, Tianjin, China
4Department of Oncology, Ruijin Hospital of Shanghai Jiaotong University, Shanghai, China
Bing Zhou, email: Zhoubingtj@sina.com
Naiqiang Cui, email: Doccuinqtj@163.com
Keywords: EGb 761, colorectal cancer, LincRNA-p21, metastasis, EZH2
Received: June 28, 2017 Accepted: July 26, 2017 Published: September 27, 2017
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.
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