槲皮素对人宫颈鳞癌顺铂耐药细胞SiHa/DDP的逆转作用研究
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篇名: 槲皮素对人宫颈鳞癌顺铂耐药细胞SiHa/DDP的逆转作用研究
TITLE: Study on Reversal Effect of Quercetin on Human Cervical Squamous Carcinoma Cisplatin-resistant Cell Line SiHa/DDP
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+20nmol/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。
ABSTRACT: 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 (0.005 μg/mL),cisplatin(2.5 μg/mL),cisplatin combined with quercetin (2.5 μg/mL cisplatin+0.005 μg/mL quercetin),quercetin combined with pathway inhibitor(0.005 μg/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 p 70S6K 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 PI 3K/Akt/mTOR signaling pathway.
期刊: 2021年第32卷第23期
作者: 冯磊,杨建敏,杨然,孙丽,董莉丽,张清伟
AUTHORS: FENG Lei,YANG Jianmin ,YANG Ran,SUN Li,DONG Lili,ZHANG Qingwei
关键字: 槲皮素;宫颈鳞癌;SiHa/DDP细胞;PI3K/Akt/mTOR信号通路;耐药性;逆转
KEYWORDS: Quercetin;Cervical squamous carcinoma ;SiHa/DDP cells ;PI3K/Akt/mTOR signaling pathway ;Drug resistance ;
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