神经酰胺增强卵巢癌顺铂敏感性的体外研究  

Study on the effect and machanism of ceramide in augmenting sensitivity of cisplatin in ovarian carcinoma

作　　者：孙莉娜[1] 徐曼[1] 胡玉芳 瞿全新[1] 

机构地区：[1]天津医科大学第一中心临床医院,天津300192 [2]天津市电力医院,天津300070

出　　处：《现代妇产科进展》2012年第7期540-543,共4页Progress in Obstetrics and Gynecology

摘　　要：目的:探讨神经酰胺增强卵巢癌顺铂敏感性的作用及机制,为筛选有效的卵巢癌顺铂耐药逆转剂提供实验依据。方法:本研究采用MTT法测定不同剂量的C6-神经酰胺(Ceramide C6)(5、10、20、40μmol/L)对卵巢癌顺铂化疗的增敏作用,以RT-PCR、Westernblot法检测Ceramide C6对肿瘤细胞Bcl-2 mRNA及其蛋白表达的影响,应用流式细胞技术观察Ceramide C6对肿瘤细胞凋亡的影响。结果:Ceramide C6对SKOV3、SKOV3/DDP细胞生长有抑制作用,与DDP联合应用时可增强DDP敏感性。SKOV3细胞中,与对照组相比,不同浓度Ceramide C6使顺铂敏感性分别增加了7.23%、20.14%、45.02%、57.75%。SKOV3/DDP细胞中,顺铂敏感性分别增加了23.08%、24.57%、45.86%、65.78%。随Ceramide C6浓度增加,SKOV3和SKOV3/DDP细胞中Bcl-2 mRNA及蛋白表达逐渐减低,差异有统计学意义(F=41.780,P=0.000;F=223.258,P=0.000;F=98.306,P=0.000;F=224.687,P=0.000)。Ceramide C6可增加SKOV3、SKOV3/DDP细胞凋亡率,差异有统计学意义(F=135.625,P=0.000;F=224.906,P=0.000)。结论:神经酰胺可能通过抑制肿瘤细胞Bcl-2 mRNA及其蛋白表达,诱导肿瘤细胞凋亡途径,增强顺铂对卵巢癌SKOV3和SKOV3/DDP细胞体外生长的抑制作用,在一定程度上逆转了卵巢癌顺铂耐药。Objective：To observe the effect and machanism of ceramide in augmenting sensitivity of cisplatin in ovarian carcinoma and to screen effective reversal agent of DDP resistance in ovarian cancer.Methods：MTT assay was used to analyze the effect of ceramide to augment sensitivity of cisplatin in ovarian carcinoma at different dosage.The effect of ceramide to expression of Bcl-2 in the mRNA and protein level was detected by RT-PCR and Western blot.Flow cytometry was used to analyze the apoptosis rate of cell.Results：The ceramide could inhibit SKOV3 and SKOV3/DDP cells and augment sensitivity of cisplatin in ovarian carcinoma when it was used combined with cisplatin.Compared with the control group,the sensitivity of cisplatin in SKOV3 cells was raised 7.23%,20.14%,45.02%,57.75%respectively with the application of different dosage of ceramide.In SKOV3/DDP cells,the sensitivity of cisplatin was raised 23.08%,24.57%,45.86%,65.78%respectively.The expressions of Bcl-2 in mRNA and protein level of SKOV3 and SKOV3/DDP were more obviously decreasing along with increasing drug concentration of ceramide（F=41.780,P=0.000;F=223.258,P=0.000;F=98.306,P=0.000;F=224.687,P=0.000）.The ceramide could increase the rate of apoptosis in SKOV3 and SKOV3/DDP cells（F=135.625,P=0.000;F=224.906,P=0.000）.Conclusions：Ceramide can enhance cisplatin inhibition of SKOV3/DDP in-vitro growth by inhibiting the expression of Bcl-2 in mRNA and protein level and further inducing apoptosis of tumor cells,and reverse cisplatin resistance of ovarian cancer in certain extent.

关 键 词：卵巢癌 SKOV3 SKOV3/DDP 顺铂 耐药 凋亡 神经酰胺 

分 类 号：R737.31[医药卫生—肿瘤]