Abstract: Objective To explore the possible mechanisms by which lidocaine inhibits the activity and cisplatin resistance of human breast cancer cells by down-regulating ATP binding cassette transporter G family member 2 (ABCG2) in vitro. Methods The effects of lidocaine on cell proliferation and cisplatin intervention were verified in MDA-MB-231 and MCF-7 cells by CCK-8, EdU and TUNEL staining. The effects of lidocaine on the expressions of ABCG2, apoptosis proteins and drug resistance proteins were detected by RT-PCR and Western blotting; the phosphorylation of PI3K/ Akt proteins was detected by Western blotting. The effects of ABCG2 overexpression on the proliferation and apoptosis of breast cancer cells after intervention with lidocaine and cisplatin were verified by CCK-8 and TUNEL. Results After intervention with 0. 5 mmol / L lidocaine, the survival rate of breast cancer cells and the number of EdU-positive cells were significantly decreased (P< 0. 05). The survival rate of cells and the Bcl-2 expression were significantly decreased, the apoptosis rate and the expression levels of cleaved-PARP, cleaved-caspase-3 and Bax were significantly increased in lidocaine group and cisplatin group when compared with the control group. These changes were more obvious in cisplatin + lidocaine group (P < 0. 05). After lidocaine treatment, the expression levels of ABCG2 mRNA and protein in cancer cells were decreased (P< 0. 05). The expression levels of ABCG2, P-gp, MRP1 and MRP2 proteins were significantly decreased in cisplatin + lidocaine group when compared with the control group (P< 0. 05). The survival rate of cells and the levels of p-PI3K/ PI3K and p-AKT / AKT were significantly decreased (P < 0. 05), while the apoptosis rate was significantly increased in lidocaine group as compared to cisplatin group (P< 0. 05). The survival rate of cells and the levels of p-PI3K/ PI3K and p-AKT / AKT were significantly increased (P < 0. 05 ), while the apoptosis rate was significantly decreased in ABCG2 overexpressed group compared to the empty plasmid group (P< 0. 05). Conclusion Lidocaine could inhibit the proliferation of breast cancer cells and increase their sensitivity to cisplatin by inhibiting ABCG2 expression and activation of PI3K/ AKT signaling pathways.

Key words: breast cancer, lidocaine, ATP binding cassette transporter G family member 2, cisplatin, drug resistance