雌二醇联合孕激素对卵巢癌细胞凋亡及micro RNA-15a表达的影响  

Effect of Estradiol Combined with Progestogen on Apoptosis of Ovarian Cancer Cell and Expression of MicroRNA-15a

作　　者：沈倩倩 罗仪 谢玉莲 韩克[2] SHEN Qianqian;LUO Yi;XIE Yulian;HAN Ke(Qingpu Branch of Zhong Shan Hospital Affiliated to Fudan University,Shanghai 201700,China;The Affiliated Drum Tower Hospital of Nanjing University,Nanjing 210000,China)

机构地区：[1]复旦大学附属中山医院青浦分院,上海201700 [2]南京大学附属南京鼓楼医院,南京210000

出　　处：《中国现代应用药学》2019年第13期1643-1647,共5页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的探讨雌二醇(E2)联合孕激素(P4)对microRNA-15a(miR-15a)表达的影响。方法采集手术中切除的卵巢癌组织标本进行细胞培养,分3个处理组:E2组,P4组和雌二醇联合孕激素(E2+P4)组。激素处理后,MTT法检测细胞存活率;流式细胞技术检测细胞凋亡与细胞周期;qRT-PCR法检测Bcl-2,Bax和miR-15a的相对表达量。结果高浓度(浓度均为10^-4mol·L^-1)的E2,P4,E2+P4能够降低卵巢癌细胞的存活率,并表现为时间依赖性;低浓度(≤10^-8mol·L^-1)E2能够提高卵巢癌细胞的存活率。与对照组相比,高浓度E2,P4和E2+P4能够增加卵巢癌细胞的凋亡率(P<0.001),并且E2+P4的作用最明显;低浓度E2能够抑制肿瘤细胞的凋亡(P<0.001)。E2,P4和E2+P4对细胞周期的影响没有统计学差异。高浓度的E2,P4和E2+P4能够下调Bcl-2的表达(P<0.05或P<0.001),上调Bax的表达(P<0.001);但是低浓度E2作用却相反。高浓度的E2+P4能够促进miR-15a的表达(P<0.001)。结论高浓度的E2,P4和E2+P4能够降低细胞的存活率促进细胞凋亡,下调Bcl-2的表达,上调Bax的表达;低浓度E2的作用则相反;高浓度的E2+P4能够促进miR-15a的表达。OBJECTIVE To evaluate the effect of estradiol(E2) combined with progestogen(P4) on expression of microRNA-15a(miR-15a).METHODS The primary ovarian cancer cells from clinical ovarian cancer tissues were isolated and cultured,and divided into 3 groups: E2 group,P4 group,E2 combined with P4(E2+P4) group.The survival rate of ovarian cancer cells after the treatment was analyzed by MTT assay.Apoptosis rate and cell cycle were measured by flow cytometry.Moreover, the relative abundance of miR-15a,Bcl-2 and Bax expressions were detected by qRT-PCR.RESULTS High concentration (10^-4 mol·L^-1) of E2,P4 and E2+P4 inhibited the survival rate of ovarian cancer cells with a time dependent manner.However, low concentration(≤10^-8 mol·L^-1) of E2 induced the survival rate of ovarian cancer cells.Compared with control group,high concentration of E2,P4 and E2+P4 induced apoptosis of ovarian cancer cells(P<0.001),and the most obvious effect of promoting apoptosis was E2+P4.However,low concentration of E2 reduced apoptosis of ovarian cancer cells(P<0.001).E2,P4 and E2+P4 had no effect on cell cycle.High concentration of E2,P4 and E2+P4 reduced the expression of Bcl-2(P<0.05 or P<0.001),but they induced the expression of Bax(P<0.001).However,the effect of low concentration of E2 was opposite. Moreover,high concentration of E2+P4 could promote the expression of miR-15a(P<0.001).CONCLUSION High concentration of E2,P4 and E2+P4 significantly inhibit the survival and promot the apoptosis,reduce the expression of Bcl-2, and induce the expression of Bax in ovarian cancer cells.However,the effect of low concentration of E2 is opposite.High concentration of E2+P4 can induce the expression of miR-15a.

关 键 词：雌二醇 孕激素 卵巢癌 BCL-2 BAX microRNA-15a(miR-15a) 

分 类 号：R965.2[医药卫生—药理学]