槲皮素对人宫颈鳞癌顺铂耐药细胞SiHa/DDP的逆转作用研究  

Study on Reversal Effect of Quercetin on Human Cervical Squamous Carcinoma Cisplatin-resistant Cell Line SiHa/DDP

作　　者：冯磊[1] 杨建敏[1] 杨然[1] 孙丽[1] 董莉丽 张清伟[2] FENG Lei;YANG Jianmin;YANG Ran;SUN Li;DONG Lili;ZHANG Qingwei(Dept.of Gynaecology,Nanyang Municipal Central Hospital,Henan Nanyang 473000,China;Dept.of Gynaecology,the First Affiliated Hospital of Luohe Medical College,Henan Luohe 462000,China)

机构地区：[1]南阳市中心医院妇科,河南南阳473000 [2]漯河医学高等专科学校第一附属医院妇科,河南漯河462000

出　　处：《中国药房》2021年第23期2875-2879,共5页China Pharmacy

基　　金：河南省医学科技攻关计划项目(No.2018021026);漯河医学高等专科学校2020年度创新创业发展能力提升工程项目(No.2020-LYZKYYB047)。

摘　　要：目的:研究槲皮素对人宫颈鳞癌顺铂耐药细胞SiHa/DDP的逆转作用。方法:测定顺铂对SiHa/DDP细胞的耐药指数以及槲皮素对SiHa/DDP细胞的逆转耐药倍数;考察槲皮素(0.005μg/mL)、顺铂(2.5μg/mL)、顺铂联合槲皮素(2.5μg/mL顺铂+0.005μg/mL槲皮素)、槲皮素联合通路抑制剂(0.005μg/mL槲皮素+20 nmol/L雷帕霉素)对SiHa/DDP细胞凋亡率及磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路相关蛋白[PI3K、Akt、mTOR、肿瘤多药耐药蛋白(P-gp)、p70核糖体S6激酶(p70S6K)]表达的影响。结果:顺铂对SiHa/DDP细胞的耐药指数为5.19,槲皮素对SiHa/DDP细胞的逆转耐药倍数为4.00。与单用顺铂和单用槲皮素比较,顺铂联合槲皮素、槲皮素联合雷帕霉素均可显著升高SiHa/DDP细胞的凋亡率(P<0.05),显著降低Akt、mTOR、p70S6K蛋白的磷酸化水平和P-gp蛋白的表达水平(P<0.05)。结论:槲皮素可逆转SiHa/DDP细胞对顺铂的耐药性,其作用机制可能与抑制PI3K/Akt/mTOR信号通路相关蛋白的表达有关。OBJECTIVE:To study the reversal effect of quercetin on human cervical squamous carcinoma cisplatin-resistant cell line SiHa/DDP.METHODS:The drug resistance index of cisplatin to SiHa/DDP cells,and the reversal resistance multiple of quercetin to SiHa/DDP cells were determined.The effects of quercetin(0.005μg/mL),cisplatin(2.5μg/mL),cisplatin combined with quercetin(2.5μg/mL cisplatin+0.005μg/mL quercetin),quercetin combined with pathway inhibitor(0.005μg/mL quercetin+20 nmol/L rapamycin)on the apoptotic rate of SiHa/DDP cells were investigated,as well as its effects on the expression of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian rapamycin target protein(mTOR)signaling pathway related proteins(PI3K,Akt,mTOR,P-gp,p70S6K).RESULTS:The resistance index of cisplatin to SiHa/DDP cells was 5.19,and reversal resistance multiple of quercetin to SiHa/DDP cells was 4.00.Compared with cisplatin alone and quercetin alone,cisplatin combined with quercetin,quercetin combined with rapamycin could significantly increase the apoptotic rate of SiHa/DDP cells(P<0.05),while decreased the phosphorylation of Akt,mTOR and p70S6K protein as well as the expression of P-gp protein(P<0.05).CONCLUSIONS:Quercetin can effectively reverse drug resistance of SiHa/DDP cells to cisplatin,which may be associated with inhibiting the expression of the protein related to PI3K/Akt/mTOR signaling pathway.

关 键 词：槲皮素 宫颈鳞癌 SiHa/DDP细胞 PI3K/Akt/mTOR信号通路 耐药性 逆转 

分 类 号：R965[医药卫生—药理学]