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利多卡因下调ABCG2抑制人乳腺癌细胞的活性和耐药性
引用本文:毕阳,文新灵,杜海亮,周荣胜. 利多卡因下调ABCG2抑制人乳腺癌细胞的活性和耐药性[J]. 医学分子生物学杂志, 2022, 19(1): 33-40. DOI: 10.3870/j.issn.1672-8009.2022.01.005
作者姓名:毕阳  文新灵  杜海亮  周荣胜
作者单位:西安交通大学第一附属医院麻醉手术部 西安市, 710061
基金项目:陕西省自然科学基金(No.2019JQ-354)。
摘    要:
目的 探究利多卡因体外下调ATP结合转运蛋白G家族成员2(ATP binding cassette transporter G family member 2,ABCG2)抑制人乳腺癌细胞的活性及顺铂耐药性的可能机制.方法 选取MDA-MB-231、MCF-7细胞,使用CCK-8、EdU、TUNEL法染色验证利多卡因对...

关 键 词:乳腺癌  利多卡因  ATP结合转运蛋白G家族成员2  顺铂  耐药性

Lidocaine Inhibits the Activity and Drug Resistance of Human Breast Cancer Cells by Down-regulating ABCG2
BI Yang,WEN Xinling,DU Hailiang,ZHOU Rongsheng. Lidocaine Inhibits the Activity and Drug Resistance of Human Breast Cancer Cells by Down-regulating ABCG2[J]. Journal of Medical Molecular Biology, 2022, 19(1): 33-40. DOI: 10.3870/j.issn.1672-8009.2022.01.005
Authors:BI Yang  WEN Xinling  DU Hailiang  ZHOU Rongsheng
Affiliation:(Department of Anesthesiology,The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an,710061,China)
Abstract:
Objective To explore the possible mechanisms by which lidocaine inhibits the ac-tivity and cisplatin resistance of human breast cancer cells by down-regulating ATP binding cassette transporter G family member 2(ABCG2)in vitro.Methods The effects of lidocaine on cell prolif-eration and cisplatin intervention were verified in MDA-MB-231 and MCF-7 cells by CCK-8,EdU and TUNEL staining.The effects of lidocaine on the expressions of ABCG2,apoptosis proteins and drug resistance proteins were detected by RT-PCR and Western blotting;the phosphorylation of PI3K/Akt proteins was detected by Western blotting.The effects of ABCG2 overexpression on the proliferation and apoptosis of breast cancer cells after intervention with lidocaine and cisplatin were verified by CCK-8 and TUNEL.Results After intervention with 0.5 mmol/L lidocaine,the surviv-al rate of breast cancer cells and the number of EdU-positive cells were significantly decreased(P<0.05).The survival rate of cells and the Bcl-2 expression were significantly decreased,the apopto-sis rate and the expression levels of cleaved-PARP,cleaved-caspase-3 and Bax were significantly increased in lidocaine group and cisplatin group when compared with the control group.These chan-ges were more obvious in cisplatin+lidocaine group(P<0.05).After lidocaine treatment,the expression levels of ABCG2 mRNA and protein in cancer cells were decreased(P<0.05).The ex-pression levels of ABCG2,P-gp,MRP1 and MRP2 proteins were significantly decreased in cispla-tin+lidocaine group when compared with the control group(P<0.05).The survival rate of cells and the levels of p-PI3K/PI3K and p-AKT/AKT were significantly decreased(P<0.05),while the apoptosis rate was significantly increased in lidocaine group as compared to cisplatin group(P<0.05).The survival rate of cells and the levels of p-PI3K/PI3K and p-AKT/AKT were significantly increased(P<0.05),while the apoptosis rate was significantly decreased in ABCG2 overex-pressed group compared to the empty plasmid group(P<0.05).Conclusion Lidocaine could in-hibit the proliferation of breast cancer cells and increase their sensitivity to cisplatin by inhibiting ABCG2 expression and activation of PI3K/AKT signaling pathways.
Keywords:breast cancer  lidocaine  ATP binding cassette transporter G family member 2  cisplatin  drug resistance
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