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纸质出版:2014
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魏昌晟,沈义军,张智,王健,周炳刚.苦参碱逆转乳腺癌耐药株MCF-7/ADR多药耐药与PI3K/AKT通道的关系[J].陆军军医大学学报(原第三军医大学学报),2014,36(22):2254-2258.
Wei Changsheng,Shen Yijun,Zhang Zhi,Wang Jian,Zhou Binggang.Matrine reverses multidrug resistance in breast cancer drug-resistant cell line MCF-7/ADR through inhibiting PI3K/AKT signal pathway[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(22):2254-2258.
魏昌晟,沈义军,张智,王健,周炳刚.苦参碱逆转乳腺癌耐药株MCF-7/ADR多药耐药与PI3K/AKT通道的关系[J].陆军军医大学学报(原第三军医大学学报),2014,36(22):2254-2258. DOI:
Wei Changsheng,Shen Yijun,Zhang Zhi,Wang Jian,Zhou Binggang.Matrine reverses multidrug resistance in breast cancer drug-resistant cell line MCF-7/ADR through inhibiting PI3K/AKT signal pathway[J].J Amry Med Univ (J Third Mil Med Univ),2014,36(22):2254-2258. DOI:
目的 探索苦参碱对乳腺癌耐药株MCF-7/ADR多药耐药的逆转作用及其机制。 方法 采用MTT法检测不同浓度苦参碱和MK2206作用MCF-7/ADR细胞24 h后的生长抑制率
以抑制率为10%的药物浓度为检测标准;用荧光RT-PCR、Western blot法检测不同浓度苦参碱作用MCF-7/ADR细胞24 h后MDR1、MRP1、PTEN、AKT基因mRNA和蛋白的表达。 结果 荧光定量RT-PCR结果显示0.6、1.2 g/L的苦参碱干预组与空白对照组相比,随着苦参碱浓度的提高,耐药基因MDR1、MRP1的表达量逐渐降低(0.6 g/L苦参碱组MDR1基因的相对表达量为0.659±0.074,MRP1基因的相对表达量为0.503±0.058,与空白对照组相比P0.01);PI3K/AKT信号通路中的PTEN基因表达量逐渐增高而AKT基因的表达量逐渐降低;相同抑制率的苦参碱组(0.6 g/L)和MK2206组(0.05 μmol/L)相比,两组降低MDR1、MRP1、AKT基因表达量的差异不明显(P0.05),MK2206组更能增高PTEN 基因的表达量。Western blot检测结果显示0.3、0.6、1.2 g/L 不同浓度苦参碱干预组与空白对照组相比,随着苦参碱浓度的提高耐药蛋白p-gp、MRP1表达量逐渐降低(0.6 g/L苦参碱组p-gp蛋白的相对表达量为0.316±0.033,MRP1蛋白的相对表达量为0.134±0.014,与空白对照组相比P0.01),PI3K/AKT信号通路中的p-AKT蛋白表达量逐渐降低,PTEN蛋白表达量逐渐增高,总AKT基因表达量变化不明显;相同抑制率的苦参碱组(0.6 g/L)和MK2206组(0.05 μmol/L)相比,苦参碱组更能降低p-gp、MRP1的蛋白表达量且更能增高PTEN的蛋白表达量,但MK2206组更能降低p-AKT的蛋白表达量,对总AKT蛋白表达量两组差异不明显(P0.05)。 结论 苦参碱具有逆转乳腺癌多药耐药的作用,其机制可能是通过抑制PI3K/AKT通道发挥作用。
Objective To explore the bioactivities of matrine and PI3K/AKT signal pathway in the reversal of multidrug resistance in breast cancer cells. Methods MTT assay was used to measure the inhibitory rate of matrine of different concentrations on breast cancer drug-resistant cell line MCF-7/ADR after 24 h. In addition
real-time RT-PCR and Western blotting were used to evaluate the mRNA and protein expression levels of MDR1
MRP1
PTEN
AKT
and p-AKT in MCF-7/ADR cells. Results Real-time RT-PCR results showed when compared with the control group
the relative expression levels of MDR1 and MRP1 in the 0.6 and 1.2 g/L matrine groups were reduced gradually (MDR1 0.659±0.074 and MRP1 0.503±0.058 in the 0.6 g/L matrine group vs MDR1 0.438±0.034 and MRP1 0.399±0.025 in the 1.2 g/L matrine group
P0.01).The relative gene expression level of AKT was also reduced gradually
but that of PTEN was increased gradually. The expression levels of MDR1
MRP1
and AKT in the cells intervened separately by 0.6 g/L matrine and 0.05 μmol/L
MK2206 didn’t have significant difference at the same inhibition rate. Western blotting results showed when compared with the control group
the expression levels of p-gp and MRP1 of the 0.3
0.6 and 1.2 g/L matrine groups were reduced gradually (p-gp 0.316±0.033 and MRP1 0.134±0.014 in the 0.6 g/L matrine group
P0.01).The protein expression of p-AKT was also reduced gradually
but that of PTEN was increased gradually. The total AKT protein expression didn’t change obviously (P0.05). At the same inhibitory rate of matrine (0.6 g/L) and MK2206 (0.05 μmol/L)
the matrine group was more effective than MK2206 group in reducing the protein expression of p-gp
MRP1 and p-AKT and increasing the protein expression of PTEN. However
the total AKT protein expression of the 2 groups didn’t have significant difference (P0.05). Conclusion The effect of matrine mediating the reversal of drug resistance of breast cancer cells probably involves PI3K/AKT signal pathway.
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