瘦素对卵巢癌细胞SKOV3增殖及凋亡的影响  

Effect of Leptin on the Proliferation and Apoptosis of Ovarian Carcinoma SKOV3 Cells

作　　者：姜霞[1,2] 薛宝瑶 谢婷婷[1] 徐晓博[1] 于月成[1] 

机构地区：[1]第四军医大学西京医院妇产科,陕西西安710032 [2]新疆生产建设兵团医院(石河子大学医学院第二附属医院)妇产科,新疆乌鲁木齐830002

出　　处：《现代生物医学进展》2015年第6期1019-1023,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(30872740)

摘　　要：目的:探讨瘦素对人卵巢癌SKOV3细胞增殖及凋亡的影响及其作用机制。方法:用不同浓度的瘦素(0、50、100、200 ng/m L)处理人卵巢癌SKOV3细胞48 h后,采用MTT法检细胞的生长;以血清饥饿诱导细胞凋亡,同时给予瘦素刺激,Annexin V/PI双染法检测细胞凋亡的变化;western blotting分析p21、cyclin D1、Bcl-2、Bax蛋白的表达水平和ERK1/2通路的活化情况。结果:瘦素以剂量依赖性的方式促进人卵巢癌SKOV3细胞的增殖,同时抑制血清饥饿诱导的细胞凋亡。瘦素处理可下调p21和上调cyclin D1的表达,抑制促凋亡分子Bax的表达和上调抗凋亡分子Bcl-2的表达。瘦素可诱导细胞中ERK1/2通路的活化,其抑制剂PD98059可明显抑制瘦素诱导的促细胞增殖和抗凋亡作用,同时伴随有cyclin D1、Bcl-2蛋白表达的下调和Bax的上调。结论:瘦素可能通过活化ERK1/2通路调节细胞有丝分裂进程,进而促进卵巢癌细胞的增殖;同时通过调节凋亡相关蛋白Bcl-2和Bax的表达抑制卵巢癌细胞的凋亡。Objective： To investigate the effect and the underlying molecular mechanism of leptin on the proliferation and apoptosis of ovarian carcinoma SKOV3 cells. Methods： After stimulation with various doses of leptin（0, 50, 100, 200 ng/m L） for 48 h,the cell proliferation rate was analyzed by MTT colorimetry. Serum deprivation was used to induce cell apoptosis in SKOV3 cells stimulated with leptin. Cell apoptosis was assessed by double staining with Annexin V and propidium iodide. The expression levels of p21, cyclin D1, Bcl-2, Bax and ERK1/2 pathway were detected by western blotting. Results： Leptin promoted the cell proliferation and dampened the apoptosis rates induced by serum deprivation in a dose-dependent manner. Furthermore, leptin treatment down-regulated the expression levels of p21, up-regulated the cyclin D1 expression. Moreover, an obvious down-regulation of Bax protein and up-regulation of Bcl-2 was confirmed in SKOV3 cell treated with leptin. Leptin dramatically induced the activation of ERK1/2 pathway,and blocking this pathway with its inhibitor PD98059 strikingly attenuated leptin-induced proliferation and anti-apoptosis effect in SKOV3 cell, concomitant with the decrease of cyclin D1 and Bcl-2 expression and increase of Bax expression. Conclusion： Leptin could promote the SKOV3 cell proliferation and inhibit the apoptosis by the activation of ERK1/2 signaling to regulate SKOV3 cell mitosis and expression levels of apoptosis-related protein.

关 键 词：卵巢癌 瘦素 增殖 凋亡 ERK1/2 

分 类 号：R737.31[医药卫生—肿瘤]