漆黄素抗卵巢癌的体内外作用研究  

The Antitumor Effects of Fisetin on Ovarian Cancer in vitro and in vivo

作　　者：孟宜波 肖超[2] 陈新莲[3] 白鹏[4] 姚远[1] 王和[1,3] 肖雪[1] 

机构地区：[1]四川大学华西第二医院妇产科出生缺陷与相关妇儿疾病教育部重点实验室,成都610041 [2]自贡市妇幼保健院妇产科,自贡643015 [3]四川大学华西第二医院遗传实验室,成都610041 [4]四川大学华西基础医学与法医学院法医物证学教研室,成都610041

出　　处：《四川大学学报（医学版）》2016年第6期830-836,共7页Journal of Sichuan University(Medical Sciences)

基　　金：国家自然科学基金(No.81001159)资助

摘　　要：目的观察漆黄素对人卵巢癌细胞株SKOV3及其移植瘤的抑制作用,探索漆黄素的抗卵巢癌作用。方法电镜直接观察漆黄素干预人卵巢癌细胞SKOV3前后的形态学变化。不同浓度梯度的漆黄素处理人卵巢癌SKOV3细胞株不同时间后,采用MTT法观察肿瘤细胞存活率,流式细胞术检测凋亡。建立人卵巢癌细胞株SKOV3的裸鼠移植瘤模型,观察漆黄素对移植瘤的生长抑制作用,通过Western blot测定Bcl-2、Bax、聚腺苷二磷酸核糖多聚酶(PARP)等蛋白的表达,探讨漆黄素抑制肿瘤生长的信号通路。结果电镜下可见漆黄素作用人卵巢癌SKOV3细胞后,细胞染色质聚集和凋亡小体产生。MTT实验显示漆黄素对人卵巢癌SKOV3细胞增殖的抑制作用具有浓度依赖性。流式细胞术显示漆黄素可诱导人卵巢癌SKOV3细胞的凋亡。裸鼠移植瘤模型显示,漆黄素干预后移植瘤体积和质量均明显下降;Western blot结果显示漆黄素作用后,移植瘤内凋亡因子Bax的表达明显增加,抗凋亡蛋白Bcl-2表达明显下降,凋亡蛋白PARP被明显剪切;上述变化尤以高浓度(400mg/kg)漆黄素干预组明显。结论漆黄素可通过抑制细胞增殖和诱导细胞凋亡,发挥抗卵巢癌作用,其有望成为一种预防和治疗卵巢癌的安全有效的天然药物。Objective We attempted to survey the inhibit effect of fisetin with human ovarian cancer cell line SKOV3 and the xenograft and the mechanism of the effect. Methods The ovarian cancer cell line SKOV3 treated by fisetin were observed directly under the transmission electronmicroscope （TEM）; MTT assay was used to determine cell viability. Flow cytometry was used to analyze the apoptosis in ovarian cancer cell line SKOV3. In addition, we established an ovarian cancer athymicnude rat model. We observed the neoplasia and progression after fisetin treatment. The proliferation and apoptosis of athymic nude rat model were evaluated hy testing Bcl-2, Bax and poly-ADP-ribose polyerase （PARP） expression through Western blot. Results The chromatin were brought together and the apoptotic bodies were detected in SKOV3 cells under transmission electron microscope after the treatment by fisetin. MTT assay indicated that fisetin inhibited ovarian cancer cell proliferation in a dose-dependent manner. The flow cytometry data demonstrated that the apoptosis might induct in SKOV3 cells after treatment by fisetin. In athymic rude rat model, under the influence of fisetin, tumor volume and tumor mass were significantly decreased. Western blot demonstrated that treatment with higher concentration of fisetin resulted in a significant decrease of Bcl-2 and a significant increase of Bax. The apoptosis proteins PARP was cut apparently. Conclusion The results provided the first insight into antitumor anti-proliferative and the induction of apoptosis efficacy of fisetin against ovarian cancer in vitro and in vivo. All data suggested a safe promising therapeutic potential of fisetin in ovarian cancer treatment.

关 键 词：卵巢癌 漆黄素 细胞凋亡 抗癌药物 

分 类 号：R285.5[医药卫生—中药学]