表皮生长因子受体信号通路与卵巢癌耐药细胞株SKOV3/DDP相关性的研究  

Relationship between epidermal growth factor receptor signaling pathway and cisplatin-resistant ovarian cancer SKOV3/DDP cells

作　　者：王娜[1] 吴小华 杨波[1] 陈亚楠[1] 许鹏宇[1] 周楠[1] 

机构地区：[1]中国人民解放军白求恩国际和平医院妇产科,河北石家庄050082

出　　处：《肿瘤》2013年第11期985-990,共6页Tumor

摘　　要：目的:探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)信号通路与卵巢癌顺铂(cisplatin,DDP)耐药细胞株SKOV3/DDP耐药相关性,及其可能的作用机制。方法:以亲本卵巢癌细胞SKOV3及DDP耐药性SKOV3/DDP细胞为研究对象;首先采用蛋白质印迹法检测EGFR信号通路在亲本株与耐药细胞中的活化情况。随后分别采用MTT法和FCM法检测单用EGFR抑制剂吉非替尼(geitinib)、DDP以及吉非替尼联合DDP对卵巢癌细胞增殖及凋亡的影响,并检测SKOV3/DDP细胞中EGFR及其下游信号通路蛋白的表达。结果:SKOV3/DDP细胞中磷酸化EGFR(phospho-EGFR,p-EGFR)(活化的EGFR)蛋白的表达量明显高于其在SKOV3细胞中的表达量(P<0.05);单独应用DDP或吉非替尼均可以抑制卵巢癌细胞的生长,吉非替尼联合DDP可明显抑制SKOV3/DDP细胞的增殖,并促进细胞凋亡,与DDP单药组相比,差异有统计学意义(P<0.05)。吉非替尼联合DDP可以明显下调p-EGFR、p-蛋白激酶B[protein kinase B,PKB(又称Akt)]和p-细胞外信号调节激酶(extracellular signal-regulated protein kinase,ERK)蛋白的表达,与DDP单药组相比,差异有统计学意义(P<0.05)。结论:吉非替尼可以增加SKOV3/DDP细胞对DDP的敏感性,其机制可能与抑制DDP诱导的EGFR及下游信号通路Akt和ERK的活性有关。Objective： To investigate the relationship between epidermal growth factor receptor （EGFR） signaling pathway and the drug resistance of cisplatin （DDP）-resistant ovarian cancer SKOV3/DDP cells. Methods： The expressions of EGFR and phospho-EGFR （p-EGFR） （active EGFR） proteins in parental SKOV3 cells and DDP-resistant SKOV3/DDP cells were examined by Western blotting. After treatment with gefitinib alone, DDP alone, and gefitinib in combination with DDP, the cellular proliferation and apoptosis of parental SKOV3 cells and SKOV3/DDP cells were detected by MTT method and flow cytometry, respectively. The expressions of EGFR, p-EGFR, Akt, phospho-Akt, extracellular signal-regulated protein kinase （ERK） and phospho-ERK proteins in SKOV3/DDP cells were examined by Western blotting. Results： The expression level of p-EGFR protein was significantly increased in SKOV3/DDP cells as compared with that in parental SKOV3 cells （P 〈 0.05）. DDP and gefitinib alone could inhibit the growth of parental SKOV3 and SKOV3/DDP cells. Gefitinib in combination with DDP could obviously induce the growth inhibition and apoptosis of SKOV3/DDP cells （P 〈 0.05, vs DDP alone）. The expression levels of p-EGFR, phospho-Akt and phospho-ERK proteins in SKOV3/DDP cells after treatment with gefitinib in combination with DDP were significantly down-regulated （P 〈 0.05, vs DDP alone）. Conclusion： Gefitinib can enhance the sensitivity of SKOV3/DDP cells to DDP. This mechanism may be related to the inhibition of activities of Akt and ERK in EGFR and its downstream signaling pathway induced by DDP.

关 键 词：卵巢肿瘤 受体 表皮生长因子 抗药性 肿瘤 顺铂 吉非替尼 

分 类 号：R735.35[医药卫生—肿瘤]