Mechanism of Sinomenine Reversing Drug Resistance of Human Breast Cancer MCF-7 Cells to Tamoxifen

OBJECTIVE To investigate the mechanism of sinomenine(SIN) reversing drug resistance of human breast cancer MCF-7 cells to tamoxifen(TAM). METHODS MCF-7/TAM persister was constructed at high concentration for a short time by stimulation induction, and the changes of drug resistance were detected by MTT assay. The proliferation inhibition of SIN and TAM on MCF-7/TAM cells was further determined by MTT assay, and the combination index of the two drugs combined was analyzed by CompuSyn software. Flow cytometry was used to detect the effects of the two drugs on the apoptosis and cell cycle of MCF-7/TAM cells; the effect of SIN on the PI3K/AKT/mTOR signaling pathway in MCF-7/TAM cells was detected by Western blotting. RESULTS The sensitivity of MCF-7/TAM cell line to TAM was significantly reduced, and the drug resistance model was successfully constructed. Both SIN and TAM alone could inhibit the proliferation of MCF-7/TAM cells, and the inhibitory effect of TAM combined with SIN on MCF-7/TAM cells was significantly enhanced. CompuSyn software analysis showed that the two drugs were synergistic. Phosphorylation levels of PI3K, Akt and mTOR in MCF-7/TAM cells were significantly higher than those in MCF-7 cells. After SIN intervention, phosphorylation levels of PI3K, Akt and mTOR in MCF-7/TAM cells were significantly reduced. CONCLUSION Sinomenine can effectively reverse the resistance of MCF-7 cells to tamoxifen, possibly by regulating the PI3K/AKT/mTOR signaling pathway.