Physcmn inhibits the metastatic potential of human colorectal cancer SW620 cells in vitro by suppressing the transcription factor SOX2  

作　　者：Yan-tao HAN Xue-hong CHEN Hui GAO Jun-li YE Chun-bo WANG 

机构地区：[1]Medical College of Qingdao University, Qingdao 266071, China

出　　处：《Acta Pharmacologica Sinica》2016年第2期264-275,共12页中国药理学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China （ No 81473384）.

摘　　要：Aim： Physcion, an anthraquinone derivative, exhibits hepatoprotective, anti-inflammatory, anti-microbial and anti-cancer activities. In this study we examined whether and how physcion inhibited metastatic potential of human colorectal cancer cells in vitro. Methods： Human colorectal cancer cell line SW620 was tested. Cell migration and invasion were assessed using a wound healing and Transwell assay, respectively. The expression levels of transcription factor SOX2 in the cells were modulated with shRNA targeting SOX2 and SOX2 overexpressing plasmid. The expression of target molecules involved in epithelial-mesenchymal transition （EMT） pro- cess and the signaling pathways was determined with Western blots or qRT-PCR. ROS levels were measured using DCF-DA. Results： Physcion （2.5, 5 mol/L） did not affect the cell viability, but dose-dependently inhibited the cell adhesion, migration and inva- sion. Physcion also inhibited the EMT process in the cells, as evidenced by the increased epithelial marker E-cadherin expression, and by decreased expression of mesenchymal markers N-cadherin, vimentin, fibronectin and α-SMA, as well as transcriptional repressors Snail, Slug and Twist. Physcion suppressed the expression of SOX2, whereas overexpression of SOX2 abrogated the inhibition of phy- scion on metastatic behaviors. Physcion markedly increased ROS production and phosphorylation of AMPK and GSK313 in the cells, whereas the AMPK inhibitor compound C or the ROS inhibitor NAC abolished the inhibition of physcion on metastatic behaviors. Conclusion： Physcion inhibits the metastatic potential of human colorectal cancer cells in vitro via activating ROS/AMPK/GSK3β signal- ing pathways and suppressing SOX2.Aim： Physcion, an anthraquinone derivative, exhibits hepatoprotective, anti-inflammatory, anti-microbial and anti-cancer activities. In this study we examined whether and how physcion inhibited metastatic potential of human colorectal cancer cells in vitro. Methods： Human colorectal cancer cell line SW620 was tested. Cell migration and invasion were assessed using a wound healing and Transwell assay, respectively. The expression levels of transcription factor SOX2 in the cells were modulated with shRNA targeting SOX2 and SOX2 overexpressing plasmid. The expression of target molecules involved in epithelial-mesenchymal transition （EMT） pro- cess and the signaling pathways was determined with Western blots or qRT-PCR. ROS levels were measured using DCF-DA. Results： Physcion （2.5, 5 mol/L） did not affect the cell viability, but dose-dependently inhibited the cell adhesion, migration and inva- sion. Physcion also inhibited the EMT process in the cells, as evidenced by the increased epithelial marker E-cadherin expression, and by decreased expression of mesenchymal markers N-cadherin, vimentin, fibronectin and α-SMA, as well as transcriptional repressors Snail, Slug and Twist. Physcion suppressed the expression of SOX2, whereas overexpression of SOX2 abrogated the inhibition of phy- scion on metastatic behaviors. Physcion markedly increased ROS production and phosphorylation of AMPK and GSK313 in the cells, whereas the AMPK inhibitor compound C or the ROS inhibitor NAC abolished the inhibition of physcion on metastatic behaviors. Conclusion： Physcion inhibits the metastatic potential of human colorectal cancer cells in vitro via activating ROS/AMPK/GSK3β signal- ing pathways and suppressing SOX2.

关 键 词：PHYSCION ANTHRAQUINONE human colorectal cancer cell line SW620 metastasis EMT process SOX2 ROS AMPK GSK3Β 

分 类 号：R9[医药卫生—药学]