Study on the chloroquine enhancing the chemotherapy sensitivity of breast cancer cells to tamoxifen

Objective: To investigate the effects and mechanism of chloroquine(CQ) enhancing the chemotherapy sensitivity of breast cancer cells to tamoxifen(TAM). Methods: The MCF-7 cells(estrogen-receptor positive breast cancer cells) were divided into the control group,TAM group,CQ group and CQ+TAM group.The control group was cultured with culture medium(no adding drug),and other groups were cultured with corresponding drugs.The survival rate of cells was determined using MTT assay.The inhibiting effects of MCF-7 cells proliferation induced by low concentration CQ,TAM and CQ combined with TAM were observed using colony formation assay.The cell apoptosis rate was determined by propidium bromide staining.The related protein expressions were detected by Western blot. Results: The survival rates of cells in TAM group,CQ group and TAM+CQ group at 24 h,48 h and 72 h of treatment were significantly lower than that in control group(P<0.01).The survival rates of cells in TAM+CQ group at 24 h,48 h and 72 h of treatment were significantly lower than that in TAM group and CQ group(P<0.01),and the survival rate of cells in TAM group at 24 h of treatment was significantly lower than that in CQ group(P<0.05).The results of colony formation assay showed that the effect of low concentration CQ on inhibiting the MCF-7 cells colony formation was not obvious,but CQ could strengthen the inhibiting effect of TAM.The differences of the apoptosis rate of cells between four groups were statistically significant(P<0.01).The apoptosis rates of cells in TAM group,CQ group and TAM+CQ group were significantly higher than that in control group(P<0.01),and the apoptosis rate of cells in TAM+CQ group was significantly higher than that in TAM group and CQ group(P<0.01).The results of Western blot showed that the protein expressions of Beclin-1 and LC3Ⅱ in TAM group increased,and the protein expression of p62 decreased with the increasing of time.Compared with the control group,the expression of LC3Ⅱprotein in TAM group significantly increased,and the expression of p62 protein in TAM group increased.Compared with the TAM group,the protein expressions of LC3Ⅱ,Beclin-1 and p62 in CQ+TAM group increased,and the expression of Bcl-2 protein in CQ+TAM group decreased. Conclusions: CQ can strengthen the chemotherapy sensitivity of breast cancer cells to TAM,the mechanism may be involved in downregulating the expression of Bcl-2 and inhibiting the autophagy.