邓琳;冯定庆;凌斌;

• 1:中日友好医院

摘要(Abstract)：

目的:探讨COX2对卵巢透明细胞癌ES细胞顺铂敏感性的影响及其机制。方法:构建慢病毒载体Lenti-COX2-EGFP,转染ES2细胞;采用Lipofectamine 3000转染sh COX2质粒,沉默ES-2细胞COX2表达,PCR及Western blot鉴定转染效率。采用CCK-8、PCR及Western blot法观察COX2对ES-2细胞增殖、耐药的影响。结果:过表达COX2促进细胞增殖,沉默COX2抑制细胞增殖(P<0.05)。上调COX2表达促进ES-2细胞对顺铂耐药,耐药指数为1.26;沉默COX2表达可提高细胞对顺铂的敏感性,逆转耐药倍数为6.68。沉默COX2可下调Vimentin、Snail和Slug表达,上调E-cadherin表达。结论:COX2可促进ES-2细胞对顺铂耐药,诱导ES2细胞EMT转化是其可能机制之一。

关键词(KeyWords)： 卵巢透明细胞癌;COX2;耐药;顺铂;EMT

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金资助项目(No:81372777,81372779)

作者(Authors): 邓琳;冯定庆;凌斌;

DOI: 10.13283/j.cnki.xdfckjz.2016.10.009

参考文献(References)：

• [1]Kajiyama H,Shibata K,Suzuki S,et al.Survival impact of adjuvant paclitaxel and carboplatin for early-stage ovarian clear-cell carcinoma with complete surgical staging[J].Gynecol Obstet Invest,2011,72(4):252-256
• [2]Wiechert A,Saygin C,Thiagarajan PS,et al.Cisplatin induces stemness in ovarian cancer[J].Oncotarget,2016,7(21):30511-30522
• [3]Jemal A,Siegel R,Xu J,et al.Cancer statistics[J].CA Cancer J Clin,2010,60(5):277-300
• [4]Ferrandina G,Zannoni GF,Ranelletti FO,et al.Cyclooxygenase2 expression in borderline ovarian tumors[J].Gynecol Oncol,2004,95(1):46-51
• [5]Chen X,Lingala S,Khoobyari S,et al.Epithelial mesenchymal transition and hedgehog signaling activation are associated with chemoresistance and invasion of hepatoma subpopulations[J].J Hepatol,2011,55(4):838-845
• [6]Ho CM,Huang YJ,Chen TC,et al.Pure-type clear cell carcinoma of the ovary as a distinct histological type and improved survival in patients treated with paclitaxel-platinum-based chemotherapy in pure-type advanced disease[J].Gynecol Oncol,2004,94(1):197-203
• [7]Utsunomiya H,Akahira J,Tanno S,et al.Paclitaxel-platinum combination chemotherapy for advanced or recurrent ovarian clear cell adenocarcinoma:a multicenter trial[J].Int J Gynecol Cancer,2006,16(1):52-56
• [8]Yang CC,Tu HF,Wu CH,et al.Up-regulation of HB-EGF by the COX-2/PGE2 signaling associates with the cisplatin resistance and tumor recurrence of advanced HNSCC[J].Oral Oncol,2016,56(1):54-61
• [9]Neumann W,Crews BC,Sarosi MB,et al.Conjugation of cisplatin analogues and cyclooxygenase inhibitors to overcome cisplatin resistance[J].Chem Med Chem,2015,10(1):183-192
• [10]Okamura H,Fujiwara H,Umehara S,et al.COX-2 overexpression induced by gene transfer reduces sensitivity of TE13 esophageal carcinoma cells to 5-fluorouracil and cisplatin[J].Anticancer Res,2013,33(2):537-542
• [11]Chung LY,Tang SJ,Sun GH,et al.Galectin-1 promotes lung cancer progression and chemo resistance by up regulating p38 MAPK,ERK,and cyclooxygenase-2[J].Clin Cancer Res,2012,18(15):4037-4047
• [12]Legge F,Paglia A,D'Asta M,et al.Phase II study of the combination carboplatin plus,celecoxib in heavily pretreated recurrent ovarian cancer patients[J].Bmc Cancer,2011,11(1):1-9
• [13]Baribeau S,Chaudhry P,Parent S,et al.Resveratrol inhibits cisplatin-induced epithelial-to-mesenchymal transition in ovarian cancer cell lines[J].PLo S One,2014,9(1):e86987
• [14]Haslehurst AM,Koti M,Dharsee M,et al.EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer[J].BMC Cancer,2012,12:91
• [15]Zlobec I,Lugli A.Epithelial mesenchymal transition and tumor budding in aggressive colorectal cancer:tumor budding as oncotarget[J].Oncotarget,2010,1(7):651-661
• [16]Iwatsuki M,Mimori K,Yokobori T,et al.Epithelial-mesenchymal transition in cancer development and its clinical significance[J].Canc Sci,2009,101(2):293-299
• [17]邓琳,冯定庆,凌斌.环氧化酶2抑制剂抗卵巢癌作用的研究进展[J].现代妇产科进展,2015,24(11):876-878
• [18]Iseri OD,Kars MD,Arpaci F,et al.Drug resistant MCF-7cells exhibit epithelial-mesenchymal transition gene expression pattern[J].Biomed Pharmacotherapy,2011,65(1):40-45
• [19]Helleman J,Smid M,Jansen MP,et al.Pathway analysis of gene lists associated with platinum-based chemotherapy resistance in ovarian cancer:the big picture[J].Gynecol Oncol,2010,117(2):170-176
• [20]Davidson B,Trope CG,Reich R.Epithelial-mesenchymal transition in ovarian carcinoma[J].Front Oncol,2012,2:33