引用本文:陈 琳,李 卫,黄国秀,韦晓英,刘 贺,庞 羽,罗珍玉,蓝盈盈,罗颖华.黄连素逆转人结肠癌细胞奥沙利铂耐药性的作用及机制[J].中国临床新医学,2021,14(10):1008-1013.
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黄连素逆转人结肠癌细胞奥沙利铂耐药性的作用及机制
陈 琳,李 卫,黄国秀,韦晓英,刘 贺,庞 羽,罗珍玉,蓝盈盈,罗颖华
530021 南宁,广西壮族自治区人民医院体检中心
摘要:
[摘要] 目的 探究黄连素(Ber)逆转人结肠癌细胞奥沙利铂(OXA)耐药性的作用及机制。方法 选用人结肠癌耐OXA细胞THC-8307/OXA进行实验,分为对照组、OXA组和Ber(5、10、20 μg/ml)+OXA组。采用倒置相差显微镜观察细胞形态,MTT法检测细胞存活率,流式细胞术检测细胞凋亡率,RT-qPCR检测MDR-1 mRNA的表达,Western blot检测P-gp、PI3K、Akt和p-Akt蛋白的表达。结果 与OXA组比较,Ber(5、10、20 μg/ml)+OXA组的细胞存活率显著降低(P<0.05),凋亡率显著升高(P<0.05);MDR-1 mRNA、P-gp蛋白、p-Akt蛋白、PI3K蛋白的表达水平及p-Akt/Akt值均显著降低(P<0.05)。其中Ber(10、20 μg/ml)+OXA组的效应显著高于Ber(5 μg/ml)+OXA组,Ber(20 μg/ml)+OXA组的效应显著高于Ber(10 μg/ml)+OXA组。OXA组与对照组的检测结果比较差异无统计学意义(P>0.05)。结论 Ber可显著逆转THC-8307/OXA细胞对OXA的耐药性,其作用机制可能与PI3K/Akt信号通路抑制,P-gp蛋白表达下调有关。
关键词:  黄连素  奥沙利铂  结肠癌  耐药性
DOI:10.3969/j.issn.1674-3806.2021.10.12
分类号:R 735.3+5
基金项目:广西壮族自治区卫生厅中医药科技专项项目(编号:GZPT13-33)
The role and mechanism of berberine in reversing oxaliplatin resistance in human colon cancer cells
CHEN Lin, LI Wei, HUANG Guo-xiu, et al.
Health Examination Center, the People′s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, China
Abstract:
[Abstract] Objective To explore the effect and mechanism of berberine(Ber) in reversing the resistance of human colon cancer cells to oxaliplatin(OXA). Methods Human colon cancer OXA-resistant cells THC-8307/OXA were selected for experiment, and they were divided into control group, OXA group and Ber(5, 10, 20 μg/ml)+OXA groups. Cell morphology was observed by inverted phase contrast microscope. Cell survival rate was detected by methyl thiazolyl tetrazolium(MTT) assay method, and cell apoptosis rate was detected by flow cytometry. Multidrug resistanc-1(MDR-1) mRNA expression was detected by real-time quantitative reverse transcription-polymerase chain reaction(RT-qPCR), and the expressions of P-glycoprotein(P-gp), phosphatidylinositol 3-kinase(PI3K), protein kinase B(Akt) and phosphorylated protein kinase B(p-Akt) proteins were detected by Western blot. Results Compared with those of the OXA group, the cell survival rates of Ber(5, 10, 20 μg/ml)+OXA groups were significantly reduced(P<0.05), and the apoptosis rates were significantly increased(P<0.05); the expression levels of MDR-1 mRNA, P-gp protein, p-Akt protein, PI3K protein, and p-Akt/Akt value were significantly reduced(P<0.05). Among them, the effects of Ber(10, 20 μg/ml)+OXA groups were significantly higher than those of Ber(5 μg/ml)+OXA group, and the effect of Ber(20 μg/ml)+OXA group was significantly higher than that of Ber(10 μg/ml)+OXA group. There were no significant differences in the detection results between the OXA group and the control group(P>0.05). Conclusion Ber can significantly reverse the resistance of THC-8307/OXA cells to OXA, and its mechanism of action may be related to the inhibition of PI3K/Akt signaling pathway and the down-regulation of P-gp protein expression.
Key words:  Berberine(Ber)  Oxaliplatin(OXA)  Colon cancer  Drug resistance