亮丙瑞林调控AMPK/COX-2通路对子宫肌瘤细胞增殖、凋亡的影响  

Effects of leuprolide regulating AMPK/COX-2 pathway on proliferation and apoptosis of uterine fibroid cells

作　　者：方娟 吴利荣[1] 刘婷婷[2] 胡昌华[1] FANG Juan;WU Lirong;LIU Tingting;HU Changhua(Department of Obstetrics,Hanyang Hospital Affiliated to Wuhan University of science and technology,Wuhan,Hubei,430053,China;Department of Gynecology,Hanyang Hospital Affiliated to Wuhan University of science and technology,Wuhan,Hubei,430053,China)

机构地区：[1]武汉科技大学附属汉阳医院产科,湖北武汉430053 [2]武汉科技大学附属汉阳医院妇科,湖北武汉430053

出　　处：《中国优生与遗传杂志》2021年第11期1553-1557,共5页Chinese Journal of Birth Health & Heredity

基　　金：武汉市新冠肺炎应急科研专项(EX20E25)。

摘　　要：目的探究亮丙瑞林对子宫肌瘤细胞增殖和凋亡及单磷酸腺苷酸活化蛋白激酶/环氧合酶-2(AMPK/COX-2)通路的影响。方法体外培养子宫肌瘤细胞,将其分为:对照组、亮丙瑞林低剂量组、亮丙瑞林中剂量组、亮丙瑞林高剂量组、高剂量+抑制剂组。噻唑蓝(MTT)法检测细胞增殖活力;AnnexinV-FITC/PI法检测细胞凋亡情况;免疫印迹(WesternBlot)检测Bcl-2相关蛋白(Bax)、B淋巴细胞瘤-2基因(Bcl-2)、半胱氨酸蛋白酶-3(Caspase-3)、磷酸化AMPK(p-AMPK)、AMPK、COX-2的表达。结果与对照组相比,亮丙瑞林低、中、高剂量组细胞增殖活力呈现下调趋势;凋亡率呈现上调趋势(P<0.05);细胞中Bax、Caspase-3与p-AMPK/AMPK蛋白表达升高,Bcl-2与COX-2蛋白表达降低,且均呈浓度依赖性(P<0.05)。与亮丙瑞林高剂量组相比,高剂量+抑制剂组细胞增殖活力、细胞中Bcl-2与COX-2蛋白表达升高,而凋亡率、细胞中Bax、Caspase-3与p-AMPK/AMPK蛋白表达降低(P<0.05)。结论亮丙瑞林可能通过激活AMPK/COX-2通路抑制子宫肌瘤细胞增殖,促进细胞凋亡。Objective To explore the effects of leuprolide on the proliferation and apoptosis of uterine fibroid cells and the adenosine 5′-monophosphate-activated protein kinase/cyclooxygenase-2(AMPK/COX-2) pathway. Methods Uterine fibroid cells were cultured in vitro and divided into: control group, low-dose leuprolide group, and medium-dose leuprolide group, high-dose leuprolide group, high-dose leuprolide + inhibitor group. MTT method was used to detect cell proliferation viability;Annexin V-FITC/PI method was used to detect cell apoptosis;Western Blot was used to detect the expression of Bcl-2 associated protein(Bax), B-cell lymphoma-2(Bcl-2), Caspase-3, phosphorylated AMPK(p-AMPK), AMPK and COX-2.Results Compared with the control group, the cell proliferation activity of the low-, medium-and high-dose leuprolide groups showed a downward trend, the apoptosis rate showed a upward-regulated trend(P<0.05);the expression of Bax, Caspase-3 and p-AMPK/AMPK proteins in the cells was increased, the expression of Bcl-2 and COX-2 proteins was reduced, and all were concentration-dependent(P<0.05). Compared with the high-dose leuprolide group, the cell proliferation activity and the expression of Bcl-2 and COX-2 proteins in the high-dose leuprolide + inhibitor group were increased, the apoptosis rate, expression of Bax, Caspase-3 and p-AMPK/AMPK proteins in cells were reduced(P<0.05). Conclusion Leuprolide may inhibit the proliferation of uterine fibroids and promote cell apoptosis by activating the AMPK/COX-2 pathway.

关 键 词：亮丙瑞林 子宫肌瘤细胞 增殖 凋亡 单磷酸腺苷酸活化蛋白激酶/环氧合酶-2通路 

分 类 号：R737.33[医药卫生—肿瘤]