Tingting Fang1, Yuan Fang2, Xiaojing Xu3, Mingyan He4, Zhiying Zhao5, Peixin Huang6, Feifei Yuan7, Mengzhou Guo8, Biwei Yang9, Jinglin Xia10. 1. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China. Electronic address: fangtt77@163.com. 2. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China. Electronic address: 17317822004@163.com. 3. Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China. Electronic address: xxjqd@126.com. 4. Department of gastroenterology, The First Affiliated Hospital of Nanchang university, Jiangxi 330006, PR China. Electronic address: hemingyan2011@163.com. 5. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China. Electronic address: zhao.zhiying@zs-hospital.sh.cn. 6. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China. Electronic address: huang.peixin@zs-hospital.sh.cn. 7. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China. Electronic address: yjndtt@126.com. 8. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China. Electronic address: gmz1202@163.com. 9. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China. Electronic address: yang.biwei@zs-hospital.sh.cn. 10. Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 201100, PR China; Minhang Hospital; Shanghai Medical School of Fudan University, Shanghai 201100, PR China. Electronic address: xiajinglin@fudan.edu.cn.
Abstract
ETHNO-PHARMACOLOGICAL RELEVANCE: Numerous studies have demonstrated the potent anticancer activity of various Chinese herbs. Actinidia chinensis Planch root (acRoots), a traditional Chinese medicine, functions as an antitumor and detoxifying agent and plays a role in diuresis and hemostasis. Treatment with acRoots confers strong inhibition of tumor growth in various forms of cancer. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis Planch root extract (acRoots) on hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Our previous study used mRNA chip analyses to identify the genes regulated by acRoots. Further analyses of the altered genes identified a key regulator of genes in response to acRoots. Here, the effects of acRoots on HCC cell proliferation, migration, invasion, and apoptosis were evaluated by cell counting, Transwell and apoptosis assays. In addition, the in vivo anti-HCC effects of acRoots were investigated using an HCC animal model. The expression of a key regulator of genes in response to acRoots was analyzed using quantitative polymerase chain reaction and western blotting. RESULTS: Treatment with acRoots (10 mg/mL) had no cytotoxicity in L02 cells and had a positive effect on L02 cell viability; however, it significantly inhibited HCC cell proliferation. Treatment with acRoots downregulated DLX2 gene expression in HCC cells, and high DLX2 expression was associated with advanced stage and poor prognosis in patients with HCC. Treatment with acRoots inhibited proliferation, invasion and migration, clonality, and the epithelial-to-mesenchymal transition, and promoted the apoptosis of HCC cells by downregulating DLX2 expression. HCC cells with higher DLX2 expression were more sensitive to acRoots. CONCLUSIONS: acRoots inhibited the malignant biological behavior of HCC cells via regulation of the epithelial-mesenchymal transition (EMT) by DLX2.
ETHNO-PHARMACOLOGICAL RELEVANCE: Numerous studies have demonstrated the potent anticancer activity of various Chinese herbs. Actinidia chinensis Planch root (acRoots), a traditional Chinese medicine, functions as an antitumor and detoxifying agent and plays a role in diuresis and hemostasis. Treatment with acRoots confers strong inhibition of tumor growth in various forms of cancer. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis Planch root extract (acRoots) on hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Our previous study used mRNA chip analyses to identify the genes regulated by acRoots. Further analyses of the altered genes identified a key regulator of genes in response to acRoots. Here, the effects of acRoots on HCC cell proliferation, migration, invasion, and apoptosis were evaluated by cell counting, Transwell and apoptosis assays. In addition, the in vivo anti-HCC effects of acRoots were investigated using an HCC animal model. The expression of a key regulator of genes in response to acRoots was analyzed using quantitative polymerase chain reaction and western blotting. RESULTS: Treatment with acRoots (10 mg/mL) had no cytotoxicity in L02 cells and had a positive effect on L02 cell viability; however, it significantly inhibited HCC cell proliferation. Treatment with acRoots downregulated DLX2 gene expression in HCC cells, and high DLX2 expression was associated with advanced stage and poor prognosis in patients with HCC. Treatment with acRoots inhibited proliferation, invasion and migration, clonality, and the epithelial-to-mesenchymal transition, and promoted the apoptosis of HCC cells by downregulating DLX2 expression. HCC cells with higher DLX2 expression were more sensitive to acRoots. CONCLUSIONS: acRoots inhibited the malignant biological behavior of HCC cells via regulation of the epithelial-mesenchymal transition (EMT) by DLX2.
Authors: Stella Baliou; Anthony M Kyriakopoulos; Demetrios A Spandidos; Vassilios Zoumpourlis Journal: Int J Oncol Date: 2020-07-14 Impact factor: 5.650