双硫仑联合顺铂对三阴性乳腺癌MDA-MB-231细胞的增殖抑制作用及其机制

doi:10.13481/j.1671-587x.20200316

Abstract

Abstract: Objective: To observe the inhibitory effect of combination of disulfiram (DSF) and cisplatin (CDDP) on the proliferation of triple-negative breast cancer (TNBC) MDA-MB-231 cells, and to explore its possible mechanism. Methods: The MDA-MB-231 cells in the logarithmic phase were divided into blank control group, DSF group, CDDP group and combination groups (60μmol·L^-1 CDDP+1,2 and 4μmol·L^-1DSF). MTT method was used to detect the survival rates of the MDA-MB-231 cells in various groups and flow cytometry was used to detect the apoptotic rates of the MDA-MB-231 cells in various groups, flow cytometry was used to detect the level of active oxygen(ROS)in the MDA-MB-231 cells in various groups, and Inductively Coupled Plasma-MassSpectrometry (ICP-MS) was used to detect the levels of Pt in the MDA-MB-231 cells in various groups. Results: The MTT method and flow cytometry results showed that after treated for 72 h, compared with 60μmol·L^-1 CDDP group,the survival rates of the MDA-MB-231 cells in combination 1 group (60μmol·L^-1CDDP+1μmol·L^-1DSF), combination 2 group (60μmol·L^-1CDDP+2μmol·L^-1DSF) and combination 3 group (60μmol·L^-1CDDP+4μmol·L^-1DSF) were decreased(P<0.05). After treated for 24 h, compared with 60μ mol·L^-1CDDP group and 2μ mol·L^-1DSF group, the apoptotic rate of the MDA-MB-231 cells in combination group (60μmol·L^-1CDDP+2μmol·L^-1 DSF) was increased (P<0.05). Compared with CDDP group, the level of ROS in the MDA-MB-231 cells in combination group(60μmol·L^-1CDDP+2μmol·L^-1 DSF) was increased (P<0.05).The ICP-MS results showed that compared with CDDP group, the level of Pt in the MDA-MB-231 cells in combination group(20μmol·L^-1CDDP+0.625μmol·L^-1 DSF) was increased (P<0.05). Conclusion: The combination of DSF and CDDP can significantly inhibit the proliferation of MDA-MB-231 cells,and its possible mechanism may be related to inhibiting the growth of tumor cells by increasing the ROS level and Pt content in the MDA-MB-231 cells.

Key words: triple-negative breast cancer, MDA-MB-231 cells, cisplatin, disulfiram, reactive oxygen species

CLC Number:

R737.9

WEN Qingyi, JIAO Miaomiao, XIE Xiao, PEN Jingyu, DONG Fengge, WEI Xue, YANG Ming. Inhibitory effect of disulfiram combined with cisplatin on triple negative breast cancer MDA-MB-231 cells and its mechanism[J].Journal of Jilin University(Medicine Edition), 2020, 46(03): 523-529.

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Inhibitory effect of disulfiram combined with cisplatin on triple negative breast cancer MDA-MB-231 cells and its mechanism

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