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EFLDO induces apoptosis in hepatic cancer cells by caspase activation in vitro and suppresses tumor growth in vivo

文献类型： 外文期刊

作者： Qu, Yan-bo 1 ; Liao, Zhi-xin 1 ; Liu, Chao 2 ; Wang, Xin-zhu 1 ; Zhang, Jing 1 ;

作者机构： 1.Southeast Univ, Sch Chem & Chem Engn, Dept Pharmaceut Engn, Nanjing 211189, Jiangsu, Peoples R China

2.Shandong Acad Agr Sci, Key Lab Agro Prod Proc Technol Shandong Prov, Inst Agro Food Sci & Technol, Jinan 250100, Shandong, Peoples R China

3.Southeast Univ, Jiangsu Prov Hitech Key Lab Biomed Res, Nanjing, Jiangsu, Peoples R China

关键词： EFLDO; Euphorbia lunulata Bge; HepG2; Apoptosis; Caspase; Xenograft; ki67

期刊名称：BIOMEDICINE & PHARMACOTHERAPY （ 影响因子：6.529； 五年影响因子：5.979 ）

ISSN： 0753-3322

年卷期： 2018 年 100 卷

页码：

收录情况： SCI

摘要： To study the apoptosis induced by EFLDO (ent-3a-formylabieta-8(14), 13(15)-dien-16,12 beta-olide), extracted from the Euphorbia lunulata Bge, in the HepG2 cell line and to study the antitumor activity of this compound in vivo, Cell viability and migration were evaluated with CCK-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt) and wound healing assays, respectively. In addition, the cell cycle was examined using flow cytometry after propidium iodide (PI) staining. Apoptosis was analyzed by using the Annexin V/PI staining assay. Pro-caspase activation and apoptosis protein expression were evaluated by western blotting. A HepG2 xenograft model in nude mice was also established to study the antitumor activity of EFLDO in vivo. Immunohistochemical analysis was used to detect the expression of Ki67 in the tumors in situ. EFLDO could induce dose-and time-dependent apoptosis in HepG2 human hepatic cancer cells. Activation of caspases 3, 8, and 9 played an important role in EFLDO-induced apoptosis in vitro. Decreased levels of Bcl-2 and Survivin and increased level of BAX were also involved in this process. Furthermore, EFLDO could inhibit HepG2 tumor growth in nude mice, and the proliferation characteristics, reflected by the Ki67 index, were suppressed significantly. The results indicated that EFLDO could induce apoptosis in hepatic cancer cells by caspase activation in vitro and suppress tumor growth in vivo.

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