白藜芦醇对人卵巢癌耐药细胞株SKOV3/DDP耐药逆转的初步研究  

Preliminary Study on Reversal of Drug Resistance of Resveratrol on Human Ovarian Cancer Cell Line SKOV3/DDP

作　　者：王慧[1] 王思思[1] 李立楠[1] 王静[1] 贺英[1] 马春星 陈丽华[1] Wang Hui;Wang Sisi;Li Linan(Department of Gynecology,the First Affiliated Hospital of Hebei North University,Zhangjiakou,Hebei 075000,China)

机构地区：[1]河北北方学院附属第一医院妇科,河北张家口075000

出　　处：《四川医学》2021年第7期664-668,共5页Sichuan Medical Journal

基　　金：河北省医学科学研究课题(编号:20200198)。

摘　　要：目的探讨白藜芦醇对人卵巢癌耐药细胞株SKOV3/DDP的耐药逆转作用及其作用机制。方法体外培养人卵巢癌顺铂耐药细胞株SKOV3/DDP,以MTT法检测单用白藜芦醇对SKOV-3/DDP的杀伤影响,确定其对此细胞株的逆转剂量;同法测定无毒剂量白藜芦醇干预后SKOV3/DDP对顺铂耐药性的变化,通过流式细胞仪检测白藜芦醇逆转剂量干预细胞株后细胞的凋亡情况,采用RT-PCR方法检测白藜芦醇处理SKOV3/DDP细胞前后MDR-1和Bcl-2基因的表达。结果回归分析得出,当白藜芦醇终活性浓度<115.68 U/ml时,对SKOV-3/DDP细胞生长无明显抑制作用,其抑制率小于10%。DDP组于24、48、72 h作用耐药SKOV3/DDP细胞的IC_(50)分别为(23.31±0.42)、(9.01±0.72)、(6.45±0.83)μg/ml,当与逆转剂量(100 U/ml)的白藜芦醇联合应用时白藜芦醇使DDP对耐药SKOV3/DDP细胞的IC_(50)均降低,差异有统计学意义(P<0.05);与24 h RF值相比,48 h和72 h RF值差异均有统计学意义(P<0.05);与对照组相比,DDP组和白藜芦醇+DDP组人卵巢癌SKOV3/DDP细胞凋亡数、MDR-1 mRNA、Bcl-2 mRNA及MDR-1/Bcl-2值与对照组比较,组间差异均有统计学意义(P<0.05),且白藜芦醇+DDP组SKOV3/DDP细胞凋亡数、MDR-1/Bcl-2值明显高于DDP组(P<0.05)。结论白藜芦醇与卵巢癌发生、发展的密切相关,可有效逆转人卵巢癌SKOV3/DDP细胞的顺铂化疗耐药性,且可通过下调MDR-1和Bcl-2的mRNA表达以减少P-gp蛋白表达及药物外排,维持细胞内的DDP浓度。Objective To explore the resistance reversal effect of resveratrol on human ovarian cancer cell line SKOV3/DDP and its mechanism.Methods Human ovarian cancer cisplatin-resistant cell line SKOV3/DDP was cultured in vitro.MTT method was used to detect killing effect of resveratrol alone on SKOV-3/DDP that reversal dose could be determined.The same method was used to determine change of SKOV3/DDP resistance to cisplatin after intervention of resveratrol at non-toxic dose.Flow cytometry was used to detect cell apoptosis.RT-PCR was used to detect MDR-1 and Bcl-2 genes before and after treatment.Results Regression analysis showed that when final active concentration of resveratrol was less than 115.68 U/ml that it had no obvious inhibitory effect on growth of SKOV-3/DDP cells and its inhibitory rate was less than 10%.IC_(50) of resistant SKOV3/DDP cells in DDP group at 24,48,and 72 h were(23.31±0.42),(9.01±0.72),(6.45±0.83)μg/ml,respectively.When compared with reversal dose(100 U/m1),resveratrol reduced IC_(50) of DDP to drug-resistant SKOV3/DDP cells with significantly difference(P<0.05).Compared with 24 hRF value,differences between 48 h and 72 h RF values were statistically significant(P<0.05).Compared with control group,numbers of apoptosis,MDR-1 mRNA,Bcl-2 mRNA and MDR-1/Bcl-2 of human ovarian cancer SKOV3/DDP cells in DDP group and resveratrol+DDP group were significantly differences(P<0.05).Number of SKOV3/DDP cell apoptosis and MDR-1/Bcl-2 in resveratrol+DDP group were significantly higher than those in DDP group(P<0.05).Conclusion Resveratrol would be closely related to the occurrence and development of ovarian cancer.It could effectively reverse cisplatin chemotherapy resistance of human ovarian cancer SKOV3/DDP cells and reduce MDR-1 and Bcl-2 mRNA by down-regulating P-gp protein and drug efflux to maintain intracellular DDP concentration.

关 键 词：白藜芦醇 卵巢癌 耐药性 逆转 

分 类 号：R737.31[医药卫生—肿瘤]