Matrine Reverses Multidrug Resistance in Eca-109/VCR Cells Via Inhibiting PI3K/Akt/mTOR Signaling Pathway

Objective To investigate the effect of matrine on multidrug resistance of Eca-100/VCR cells. Methods Methyl thiazolyl tetrazolium assay was used to assess the cytotoxic activity of matrine to Eca-109/VCR cells and the sensitivity of cells to Vincristine (VCR). Then Eca-109/VCR cells were divided into four groups: control group, matrine group, VCR group and matrine combined with VCR group. Immunofluorescence staining was used to detect P-gp protein expression. Western blot was used to detect MRP1, P-gp, Beclin 1, p62(SQSTM1), LC3, p-mTOR, p-Akt and p-p70S6K protein expression. MDR1 mRNA expression was detected by RT-qPCR. Transmission electron microscopy was used to detect the ultra structural changes. Results Matrine could reverse the resistance of Eca-109/VCR cells to VCR with a reversal index of 3.52. Compared with the other groups, the expression of LC3-II, Beclin 1 increased while P-gp, MRP1, p62(SQSTM1), p-mTOR, p-Akt and p-p70S6K significantly decreased in matrine+VCR group (P<0.05). The expression of MDR1 mRNA decreased in Eca-109/VCR cells treated with matrine, VCR or their combination. The number of autophagic vacuoles in Eca-109/VCR cells increased after matrine treatment. Conclusion Matrine has anticancer and anti multidrug resistance functions in Eca-100/VCR cells, and it may be produced by promoting autophagy which mediated through PI3K/Akt/mTOR signaling pathway.