整合素α5与卵巢癌铂类耐药信号传导通路的相关研究  

Study on the correlation between integrin α5 and platinum-resistance signal transduction pathway in ovarian cancer

作　　者：韦露薇 陈国伟 李莉莉 李力[2] WEI Luwei;CHEN Guowei;LI Lili;LI Li(Department of Gynecology,Liuzhou Workers′Hospital,Liuzhou 545001,Guangxi,China;Department of Gynecologic Oncology,the Affiliated Tumor Hospital of Guangxi Medical University,Nanning 530021,Guangxi,China)

机构地区：[1]柳州市工人医院妇科,广西柳州545001 [2]广西医科大学附属肿瘤医院妇瘤科,南宁530021

出　　处：《中国性科学》2022年第9期63-68,共6页Chinese Journal of Human Sexuality

基　　金：广西自然科学基金项目(2018GXNSFBA138052);国家自然科学基金项目(82060470)。

摘　　要：目的 探究整合素α5(ITGA5)在铂类耐药卵巢癌中的表达,探讨其与卵巢癌铂类耐药信号传导通路的关系。方法 采用实时荧光定量聚合酶链反应(qRT-PCR)法检测卵巢癌铂类敏感及铂类耐药组织中ITGA5的表达,同时检测卵巢癌SKOV3、A2780细胞及铂类耐药SKOV3/顺铂(DDP)、A2780/DDP细胞中ITGA5的表达量和DDP干预后裸鼠移植瘤组织中ITGA5的表达量;随后将卵巢癌SKOV3/DDP细胞分为siITGA5-SKOV3/DDP组(ITGA5沉默组)和siNC组(阴性对照组),采用PathScan~? Antibody Array Kit、RTK Signaling Antibody Array Kit检测两组细胞信号通路差异基因的表达。结果 ITGA5在卵巢癌铂类耐药组织及铂类耐药SKOV3/DDP、A2780/DDP细胞中的表达高于铂类敏感组织及亲本细胞(P<0.05)。在裸鼠移植瘤模型中,随着DDP干预次数增多,敏感和耐药组织中ITGA5 mRNA的表达均随DDP干预次数的增加逐渐下降(P<0.05)。与阴性对照组相比,ITGA5沉默组细胞EGFR/ErbB1、HER2/ErbB2、FGFR1、TrkA/NTRK1、ALK、P44/42 MAPK (ERK1/2)、Akt、Bad、HSP27、p53、p38 MAPK、SAPK/JNK、PARP、Caspase-3、Caspase-7、IkBa、Chk1、IkBa、EphB4和Akt/PKB/Rac蛋白表达水平升高,IGF-IR蛋白表达水平降低(P<0.05)。结论 ITGA5可能是卵巢癌顺铂耐药的潜在信号分子,其可能通过ECM-ITGA-Akt-MAPK这一途径参与卵巢癌细胞对DDP的耐药。Objective To investigate the expression of integrin α5(ITGA5) in platinum-resistant ovarian cancer and its relationship with the signal transduction pathway of platinum-resistant ovarian cancer.Methods Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR) was used to detect the expression of ITGA5 in platinum-sensitive and platinum-resistant ovarian cancer tissues.The expression of ITGA5 in SKOV3 and A2780 ovarian cancer cells and platinum-resistant SKOV3/cisplatin(DDP) and A2780/DDP cells was detected,and the expression of ITGA5 in xenograft tumor tissues of nude mice after DDP intervention.Subsequently,ovarian cancer SKOV3/DDP cells were divided into siITGA5-SKOV3/DDP group(ITGA5 silencing group) and siNC group(negative control group).PathScan^(?) Antibody Array Kit and RTK Signaling Antibody Array Kit were used to detect the expression of differentially expressed genes in signaling pathways between the two groups.Results The expression of ITGA5 in platinum-resistant ovarian cancer tissues and platinum-resistant SKOV3/DDP and A2780/DDP cells was significantly higher than that in platinum-sensitive tissues and cells(P<0.05).In the xenograft model of nude mice,the expression of ITGA5 mRNA in both sensitive and drug-resistant tissues decreased with the increase of DDP intervention times(P<0.05).Compared to the inegative control group,EGFR/ErbB1,HER2/ErbB2,FGFR1,TrkA/NTRK1,ALK,P44/42 MAPK(ERK1/2),Akt,Bad,HSP27,p53,P38 MAPK,SAPK/JNK,PARP,Caspase-3,Caspase-7,IkBa,Chk1,IkBa,EphB4 and Akt/PKB/Rac in ITGA5 silencing group,while the protein expression level of IGF-IR was decreased(P<0.05).Conclusions ITGA5 may be a potential signaling molecule of cisplatin resistance in ovarian cancer cells,and may be involved in DDP resistance of ovarian cancer cells through the ECM-ITGA5-Akt-MAPK pathway.

关 键 词：卵巢癌 整合素Α5 信号传导通路 

分 类 号：R711[医药卫生—妇产科学]