炎性相关因子诱导卵巢癌细胞增殖信号和蛋白酶表达的实验研究  

Inflammatory associated factors induce the expression of cell proliferation signals and proteases in ovarian cancer cells

作　　者：李莉[1] 刘洁[1] 艾贵海[1] 秦锦龙[1] 丁金晔 程忠平 LI Li;LIU Jie;AI Gui-hai;QIN Jin-long;DING Jin-ye;CHENG Zhong-ping(Dept.of Gynecology and Obstetrics,Tenth People s Hospital,Tongji University School of Medicine,Shanghai 20072,China)

机构地区：[1]同济大学附属第十人民医院妇产科

出　　处：《同济大学学报（医学版）》2019年第5期563-569,共7页Journal of Tongji University(Medical Science)

基　　金：国家自然科学基金面上项目(81874104)

摘　　要：目的研究炎性微环境中脂多糖(lipopolysaccharide,LPS)和肿瘤坏死因子-α(tumor necrosis factor,TNF-α)诱导卵巢癌细胞增殖信号及蛋白酶的表达。方法采用实时荧光定量PCR(real-time PCR)和Western印迹法分别检测对照组、LPS和TNF-α刺激组以及添加LPS和TNF-α抑制剂组卵巢癌细胞中的细胞增殖信号及蛋白酶的mRNA和蛋白表达情况;并通过ELISA检测这些细胞上清液中蛋白酶的表达。结果LPS和TNF-α刺激组中的炎性增殖信号JNK、p38、ERK和NF-κB/p65及蛋白酶(基质金属蛋白酶-9、中性粒细胞蛋白酶和组织蛋白酶)的mRNA明显高于对照组(P<0.05),且该应答可以被LPS和TNF-α拮抗剂所抑制。LPS和TNF-α处理组诱导细胞增殖信号相关蛋白的激活及蛋白酶的表达,同时此效应可以被相关受体拮抗剂所抑制。结论肿瘤微环境中的炎性相关因子LPS和TNF-α通过诱导卵巢癌细胞炎性增殖信号及蛋白酶的表达,分别从促进细胞炎性增殖及细胞侵袭转移能力方面影响卵巢癌的发生发展。Objective To investigate the effect of inflammatory factors on expression of cell proliferation signals and proteases in ovarian cancer cells.Methods The ovarian cancer HEY cells were treated with LPS/TNF-αand/or LPS/TNF-αreceptor inhibitor,the mRNA and protein expression of cell proliferation signals and proteases in HEY cells were detected by real-time PCR and Western blot,respectively.ELISA was performed to exam the release levels of proteases of cell supernatants.Results The mRNA expression of cell proliferation signals(including JNK,p38,ERK and NF-κB/p65)and proteases(including matrix metalloproteinase-9,neutrophil elastase and cathepsin-G)in the LPS/TNF-αtreatment groups were significantly higher than in non-treated cells(P<0.05),and this response was blocked by LPS/TNF-αinhibitor.The LPS/TNF-αtreatment group stimulated the activation of cell proliferation signal-related proteins and induced the proteins expression of proteases,and the effects were suppressed by their inhibitor.Conclusion Inflammatory associated factors LPS and TNF-αcan induce the expression of proliferation signals and proteases in the tumor microenvironment,which may enhance the proliferation and invasion of ovarian cancer calls.

关 键 词：卵巢癌 肿瘤炎性微环境 脂多糖 肿瘤坏死因子-Α 基质金属蛋白酶-9 

分 类 号：R737.31[医药卫生—肿瘤]