IL-6对卵巢癌细胞迁移和侵袭影响及机制探讨  

Effect of IL-6 on migration and invasion of ovarian cancer cells and its mechanism

作　　者：方艳惠 赵喜娃[2] 安丽沙 FANG Yan-hui1, ZHAO Xi-wa1, AN Li sha2(1. Fourth Hospital of Hebei Medical University, Shijiazhuang 050000,P. R. China 2. Department of Obstetrics and Gynecology, Handan Maternal and Child Health Hospital, Handan 056001 ,P. R. Chin)

机构地区：[1]河北医科大学第四医院东院区妇科,河北石家庄050000 [2]河北医科大学第四医院妇科,河北石家庄050000 [3]邯郸市妇幼保健院妇产科,河北邯郸056001

出　　处：《中华肿瘤防治杂志》2018年第16期1156-1162,共7页Chinese Journal of Cancer Prevention and Treatment

摘　　要：目的由于卵巢癌早期无法诊断以及在腹腔内的高转移性导致该病具有较高的死亡率。白细胞介素6(IL-6)是一种重要的炎性因子,其高表达及异常信号与上皮性卵巢癌的预后密切相关。本研究旨在探讨IL-6对卵巢癌A2780和SKOV-3细胞迁移和侵袭能力的影响以及相关的信号通路。方法采用划痕以及基质胶侵袭实验等检测IL-6对人卵巢癌细胞A2780及SKOV-3的迁移、侵袭能力的影响;实时荧光定量PCR和蛋白质印迹法分析IL-6对基质金属蛋白酶2(MMP-2)和基质金属蛋白酶9(MMP-9)表达,以及对p38和细胞核因子κB(NF-κB)信号通路的影响;将p38和NF-κB信号通路抑制剂分别作用于A2780和SKOV-3细胞,基质胶侵袭实验分析在IL-6处理下抑制剂对细胞侵袭能力的影响,蛋白质印迹法检测MMP-2和MMP-9的表达。结果 IL-6处理24h后,卵巢癌细胞A2780和SKOV-3伤口愈合能力分别为65.51±6.09和58.21±5.14,相对于对照组的24.51±2.27和18.86±2.02增强,t值分别为15.093和15.582,均P<0.05;A2780和SKOV-3侵袭能力分别为3.42±0.25和6.50±0.54,相对于对照组的1.01±0.05和1.05±0.04增强,t值分别为6.125和17.792,均P<0.05。A2780和SKOV-3细胞中,MMP-2的mRNA水平在IL-6处理下分别增加2.6和2.1倍,MMP-9分别增加1.7和1.3倍;MMP-2的蛋白水平分别增加2.5和1.9倍,MMP-9分别增加1.6和1.5倍,P<0.05。IL-6可显著增加A2780和SKOV-3细胞中p38磷酸化,分别增加了4.1和3.7倍;p65的磷酸化分别增加了2.9和2.6倍,P<0.05。与IL-6处理相比,联合SB203580抑制剂作用于A2780和SKOV-3细胞后侵袭能力分别下降为80.9%和90.3%,联合PDTC抑制剂作用后侵袭能力分别下降为81.1%和89.8%,P<0.05;同时抑制MMP-2和MMP-9的表达,差异均有统计学意义,P<0.05。结论 IL-6通过p38/NF-κB信号通路协调激活基质金属蛋白酶的表达促进卵巢癌细胞的迁移和侵袭,为卵巢癌的治疗提供可靠靶点。OBJECTIVE Ovarian cancer has a higher mortality rate due to early inability to diagnose and high metastasis in the abdominal cavity. Interleukin-6（IL-6） is an important inflammatory factor, and its high expression and ab- normal signal are closely related to the prognosis of epithelial ovarian cancer. The aims of this study was to investigate the effect of IL-6 on the migration and invasion of A2780 and SKOV-3 cells in ovarian cancer and the related signaling path- way. METHODS The effect of IL-6 on the migration and invasion abilities of human ovarian cancer cells A2780 and SK- OV-3 were detected by woundhealing and invasion assays. The methods of real-time quantitative PCR and Western Blot were used to analyze the effect of IL-6 on MMP 2 and MMP-9 expression and p38/ NF-κB signaling pathway. The A2780 and SKOV-3 ceils were separately treated with the p38/NF-κB signaling pathway corresponding inhibitors, the effects of inhibitors on cell invasion capacities were detected by invasion assays. Western Blot method was used to analyze the effects of inhibitors on MMP-2 and MMP 9 under IL-6 treatment. RESULTS The wound healing abilities of ovarian cancer cells A2780 and SKOV-3 （A2780 ： 65.51±6.09, SKOV-3 ： 58.21±5.14） were significantly enhanced （ t= 15. 093, 15. 582,P〈0.05） compared with the group without IL-6 treatment （A2780,24.51±2.27;SKOV-3,18.86＋2.02）, and the invasion ability of ovarian cancer cells A2780 and SKOV-3 （A2780：3.42 ±0.25, SKOV-3：6.50±0.54） were signifi cantly enhanced （t=6. 125±17. 792, P〈0.05） compared with the group without IL-6 treatment （A2780：1.01±0.05,SKOV-3~I. 05±0.04）. Interestingly, the mRNA levels and protein levels of MMP-2 and MMP-9 in A2780 and SKOV-3 cells were increased significantly with IL-6 treatment. Moreover, IL-6 also significantly increased the phosphorylation of p38（4.1 times and 3.7 times） and p65（2.9 times and 2.6 times） in the A2780 and SKOV-3 cells. Compared with IL-6 treatment, invasion capacity combination wi

关 键 词：卵巢癌 IL-6 基质金属蛋白酶 p38/NF-κB 细胞迁移 细胞侵袭 

分 类 号：R737.31[医药卫生—肿瘤]