血根碱对乳腺癌阿霉素耐药株MCF-7/ADR的逆转作用及机制分析  

The reversal effect of sanguinarine on doxorubicin-resistant breast cancer strain MCF-7/ADR and its mechanism

作　　者：赵敏[1] 蒋晓春 陈芬 Zhao Min

机构地区：[1]浙江中医药大学附属第一医院,310006

出　　处：《浙江临床医学》2022年第5期643-645,共3页Zhejiang Clinical Medical Journal

基　　金：浙江省公益性基础研究项目(LCD19C04007)。

摘　　要：目的 探讨血根碱对乳腺癌耐药细胞株的耐药逆转作用及机制.方法 CCK8法检测亲本MCF-7细胞、耐药株MCF-7/ADR细胞及血根碱处理后耐药株IC_(50)的变化;罗丹明123实验鉴定重要耐药蛋白P-gp功能变化;Western blot法鉴定亲本细胞、耐药细胞、血根碱和AKT激动剂IGF-1处理后相关蛋白(P-AKT、AKT、P-gp)的表达水平.结果 与亲本MCF-7细胞相比,ADR、CTX和5-FU对MCF/ADR耐药细胞的IC_(50)明显增高;罗丹明123在MCF-7/ADR细胞胞内蓄积减少,外排功能加强;MCF-7/ADR耐药细胞P-gp表达明显升高.8μmol/L血根碱能显著降低MCF-7/ADR细胞的IC_(50)和罗丹明123外排功能,并能降低P-gp蛋白的表达.8μmol/L血根碱作用后,AKT通路活性明显被抑制,P-gp蛋白表达明显降低;进一步在血根碱作用后应用AKT通路激动剂IGF-1,则P-gp蛋白表达明显升高.结论 MCF-7/ADR细胞具有多药耐药特性,其耐药机制主要为提高P-gp蛋白的表达;血根碱能明显逆转MCF-7/ADR细胞的多药耐药性,其耐药逆转机制主要是通过抑制AKT通路活性进而降低P-gp蛋白表达实现的.Objective To explore the reversal efet and mechanism of Sanguiarine on the breast cancer drug-resistant cell line.Methods The change of ICsoof MCF-7.MCF-7/ADR and MCF-7/ADR cell afer Sanguinarine treatment were examined by CC K-8 asay,the change of important resistance protein P-gP func tion was idenified by Rhodanine123 asay,the expression levels of P-AKT AKT,P-gp in MCF-7,MCF-7/ADR,MCF-7/ADR+San and MCF-7/ADR+San+IGF-I were detected by Western blot amalysis.Results Compared to parental MCF-7 cell line,the IC_(50) of ADR,5-FU and CTX to MCF-7/ADR cell was markedly increased,the Rhodainel23 itrtacllular accumulaion was decreased and eflux was enhanced in MCF/ADR cell,the expression of P-P protcin in MCF-7/ADR resistat cell was signifcantly uprcgulated.The IC_(50),R hodamine eflux and expresion of P-gp protein was conspicuously decreased by 8μmol/L Sanguinarine.Afer 8μmol/L Sanguinarine treatment,AKT pathway was inhibited and the expression ofP-gP protein was reduced.Furthermore,we used AKT activator IGF-1 ater Sanguinarine pre-treatmnent,the expression of P-gp protein was markedly increased.Conclusion MCF-7/ADR cll line pssesses mulidrug reistance(MDR)property and the mechanism of MDR may be related to upregulation of P-gp protein.Sanguinarine can reverse the MDR property of MCF-7/ADR cell and the mechanism of MDR-reversion may be referred to reduce the expression of P-gP protein via inhibiing AKT pathway.

关 键 词：血根碱 乳腺癌 多药耐药 耐药逆转 AKT通路 

分 类 号：R73[医药卫生—肿瘤]