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.
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:
Matrine reverses multidrug resistance in breast cancer drug-resistant cell line MCF-7/ADR through inhibiting PI3K/AKT signal pathway
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.