Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Laboratory of stem cell & tissue engineering, West China Second University Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
BMC Complement Altern Med. 2018 Mar 15;18(1):91. doi: 10.1186/s12906-018-2127-7.
The anti-tumor activities of Natural compounds and their derivatives are of great interest to pharmaceutical industries. Fisetin is one of prospective natural compounds in this regard but unfortunately with poor hydrophilicity.
The effects of unmodified and modified fisetin in cultured ovarian cancer cells were compared by transmission electronmicroscopy to determine apoptotic bodies, MTT assay to quantitate cell numbers, and fluorescence activated cell sorting analyse of various markers to determine the apoptotic state. In addition, the efficacy of fisetin and fisetin-micelles in vivo was determined by using immunocompromised mice. Apoptosis was measured by established markers using both western blot analysis and immunochemistry. Angiogenesis in a xenograft mouse model carring SKOV3 cells was evaluated by color Doppler ultrasound and immunohistochemistry.
Multiple lines of evidence indicated that fisetin and fisetin micelles induce apoptosis in ovarian cancer cells in a dose-dependent manner. Histological analysis, terminal deoxynucleotidyltransferase-mediated nick-end labeling assay, western blot, immunohistochemical detection and microvessel density detection demonstrated that fisetin and fisetin micelles induced increased tumor apoptosis, proliferation suppression and antiangiogenesis activities.
As far as we know, the present study is the first time to demonstrate the potency of both fisetin and fisetin micelles inducing apoptosis in ovarian cancer cells. Further studies will be needed to validate the therapeutic potential of fisetin and fisetin micelles in ovarian cancer treatment.
天然化合物及其衍生物的抗肿瘤活性引起了制药行业的极大兴趣。根皮素是这方面有前景的天然化合物之一，但不幸的是其亲水性较差。
通过透射电子显微镜比较未修饰和修饰的根皮素在培养的卵巢癌细胞中的作用，以确定凋亡小体；通过 MTT 测定法定量细胞数量；通过荧光激活细胞分选分析各种标记物来确定凋亡状态。此外，还使用免疫功能低下的小鼠来确定根皮素和根皮素胶束的体内疗效。通过使用Western blot 分析和免疫化学两种方法，使用已建立的标记物来测量凋亡。通过彩色多谱勒超声和免疫组织化学评估携带 SKOV3 细胞的异种移植小鼠模型中的血管生成。
多条证据表明，根皮素和根皮素胶束以剂量依赖的方式诱导卵巢癌细胞凋亡。组织学分析、末端脱氧核苷酸转移酶介导的缺口末端标记测定、Western blot、免疫组织化学检测和微血管密度检测表明，根皮素和根皮素胶束诱导肿瘤凋亡增加、增殖抑制和抗血管生成活性。
据我们所知，本研究首次证明了根皮素和根皮素胶束在诱导卵巢癌细胞凋亡方面的效力。需要进一步研究来验证根皮素和根皮素胶束在卵巢癌治疗中的治疗潜力。
