Effect of chloroquine on proliferation of triple negative breast cancer MDA-MB-231 cells and its underlying mechanism / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To explore the effect of chloroquine(CQ) on the proliferation of triple negative breast cancer MDA-MB-231 cells and its underlying mechanism. METHODS MDA-MB-231 cells were treated with CQ 20, 40 and 80 μmol • L-1 for 24 and 48 h, respectively. CCK-8 and colony formation assays were used to detect the proliferation of MDA-MB-231 cells. Flow cytometry was employed to analyze cell cycle and apoptosis. Western blotting was used to detect the expressions of cell cycle proteins, apoptosis-related proteins and autophagy-related markers. RESULTS CQ 20, 40 and 80 μmol • L-1 could effectively inhibit the proliferation of MDA-MB-231 cells both at 24 and 48 h. Compared with the cell control group, the percentage of G0/G1 cells significantly increased when exposed to CQ 20 and 40 μmol•L-1 for 24 h (P<0.01), the percentage of G2/M cells increased (P<0.01) and the apoptosis was relatively up-regulated (P<0.01) after treatment with CQ 80 μmol • L-1 for 24 h. The apoptosis was significantly elevated after exposure to CQ 20, 40 and 80 μmol•L-1 for 48 h in a concentration-dependent manner (P<0.05). After treatment with CQ, the expression of cell cycle proteins, such as cyclin-dependent kinase-2 (CDK2), CDK4 and cyclin D3, was decreased (P<0.01), the expression of apoptosis-related proteins cleaved-caspase 3 and cleaved- poly-ADP-ribose polymerase was both elevated (P<0.01), and the expression of autophagy-related markers microtubule-associated proteinl light chain 3 and SQSTM1 was both increased (P<0.01). CONCLUSION CQ can effectively suppress the proliferation of TNBC MDA-MB-231 cells by inhibiting autophagy, inducing cell cycle arrest and promoting apoptosis.