HMMR-AS1介导EMT在上皮性卵巢癌顺铂获得性耐药中的作用  

HMMR-AS1 Mediates the Role of EMT in Acquired Cisplatin Resistance in Epithelial Ovarian Cancer

作　　者：王冉冉 董珊珊 龙瀛 丁麒 任华益 曾勇 WANG Ranran;DONG Shanshan;LONG Ying;DING Qi;REN Huayi;ZENG Yong(Translational Medicine Center;Department of Pharmacy,Hunan Cancer Hospital / the Affiliated Cancer Hospital of Xi-angya School of Medicine,Central South University,Changsha,Hunan,410013,Chin;The Affiliated Cancer Hospital of Xiangya School of Medicine,Central South University,Changsha,Hunan,410013,China)

机构地区：[1]湖南省肿瘤医院/中南大学湘雅医学院附属肿瘤医院转化医学中心,湖南长沙410013 [2]中南大学湘雅医学院附属肿瘤医院,湖南长沙410013 [3]湖南省肿瘤医院/中南大学湘雅医学院附属肿瘤医院药学部,湖南长沙410013

出　　处：《肿瘤药学》2018年第4期498-504,共7页Anti-Tumor Pharmacy

基　　金：国家自然科学青年科学基金项目(81201730,81703005);湖南省自然科学青年基金项目(2018JJ3311);湖南省卫生计生委科研计划项目(B2017098)

摘　　要：目的探讨上皮性卵巢癌(EOC)患者组织中HMMR-AS1表达对细胞侵袭、迁移能力及药物敏感性的影响,分析其与患者预后的关系。方法采用实时荧光定量PCR(q RT-PCR)、Western blot法检测人卵巢癌细胞株SKOV3、A2780和顺铂耐药细胞株SKOV3/DDP中HMMR-AS1及上皮-间质转化(EMT)标志物E-cadherin、vimentin的表达情况,Transwell实验检测SKOV3和耐药株SKOV3/DDP的侵袭、迁移能力。收集40例EOC患者的肿瘤组织石蜡标本,q RT-PCR检测标本中HMMR-AS1表达情况,同时电话随访患者5年,采用Kaplan-Meier(KM)法、Cox风险回归模型进行生存分析,探讨HMMR-AS1表达与EOC临床病理特征的关系。结果 (1)HMMR-AS1和vimentin在SKOV3细胞中的表达显著高于A2780细胞(P<0.01),而E-cadherin的表达显著低于A2780细胞(P<0.01);(2)HMMR-AS1在耐药株SKOV3/DDP中的表达明显高于SKOV3,且耐药株SKOV3/DDP的侵袭、迁移能力显著增强;(3)HMMR-AS1高表达、中/低分化、临床分期Ⅲ/Ⅳ期、淋巴结转移阳性是EOC患者预后的独立危险预测因素。结论 HMMR-AS1可能通过介导EMT发生,提高EOC细胞的侵袭、迁移能力,并降低其对化疗药物的敏感性。Objective To investigate the effects of HMMR-AS1 expression on the invasion, migration and drug sensitivity of epithe- lial ovarian eaneer （EOC） eells, and analyze its relationship with the prognosis of EOC patients. Methods Real-time PCR （qRT-PCR） and Western-blot （WB） were used to analyze the expression of HMMR-AS1, E-eadherin and vimentin in human ovarian eaneer eell line SKOV3, A2780 and eisplatin-resistant eell line SKOV3/DDP. The invasion and migration ability of SKOV3 and SKOV3/DDP were eom- pared by Transwell assay. The HMMR-AS 1 expressions of the collected paratt^n-embedded specimens of 40 E OC patients were detected by qRT-PCR, and these patients were followed up for 5 years by telephone. Survival analysis was performed using Kaplan-Meier （KM） method and Cox risk regression model. The relationship was also investigated between HMMR-AS1 expression and clinical pathological features of EOC. Results （1） The expression of HMMR-AS1 and vimentin in SKOV3 eells was higher than in A2780 eells, while the expression of E-eadherin in SKOV3 eells was relatively lower than in A2780 eells （P〈0.01）. （2） The expression level of HMMR-AS1 was signifieantly higher in SKOV3/DDP cells than in SKOV3 cells, and the invasion and migration ability of drug-resistant strain SKOV3/DDP was enhanced.（3） The high expression of HMMR-AS1, medium/low-differentiated cell type, clinical stage Ⅲ/IV, and lymph node metastasis were inde- pendent risk predictors of prognosis in patients with EOC. Conclusion HMMtl-AS1 may mediate the oeeun＇enee of epithelial-mesenehymal transition （EMT）, thereby enhance the invasion and migration of EOC cells and reduce the sensitivity of EOC to chemotherapy drugs.

关 键 词：HMMR-ASl 上皮性卵巢癌 上皮-间质转化 耐药 

分 类 号：R737.31[医药卫生—肿瘤]