优降宁与多柔比星协同抑制小鼠三阴性乳腺癌4T-1细胞的增殖和迁移

目的研究赖氨酸特异性去甲基化酶1(lysine-specifc demethylase 1,LSD1)抑制剂优降宁(Pargyline)与化疗药物多柔比星(Doxorubicin)联合应用对小鼠三阴性乳腺癌4T-1细胞增殖、迁移和侵袭的影响。方法体外实验以小鼠三阴性乳腺癌4T-1细胞为模型,以CCK-8法、乳酸脱氢酶释放实验、Chou-Talay法、划痕实验、Transwell实验、Western blot等试验方法检测两药联合对4T-1细胞增殖、侵袭、迁移的影响;构建荷瘤小鼠模型研究两药联用对4T-1细胞体内增殖的影响。结果优降宁和多柔比星可有效抑制4T-1细胞增殖、迁移和侵袭,两药联用具有协同效应,且无明显细胞毒性。体内实验证明,与单用药组相比,两药联用可明显抑制乳腺癌的体内增殖并延长三阴性乳腺癌4T-1细胞荷瘤小鼠的生存期。结论优降宁与多柔比星联合应用对小鼠乳腺癌4T-1细胞的增殖、迁移和侵袭具有协同抑制效应,具有用于临床三阴性乳腺癌治疗的潜在价值。

Effects of combination of pargyline and doxorubicin on proliferation and migration of tripple negative breast cancer 4T-1 cells

Aim To study the combination of lysine-specifc demethylase 1(lysine-specifc demethylase 1,LSD1)inhibitor pargyline and the chemotherapy drug doxorubicin on the proliferation,migration and invasion of murine triple negative breast cancer 4T-1 cells.Methods In vitro,the effect on the proliferation,invasion and migration of 4T-1 cells of the combination of these two drugs were detected with CCK-8 method,lactate dehydrogenase release test,Chou-Talay method,Scratch test,Transwell assay,Western blot and etc.Tumor-bearing mice were used to investigate the combined effect of these two drugs on the proliferation of 4T-1 cells in vivo.Results The combination of pargyline and doxorubicin effectively inhibited the proliferation,migration and invasion of 4T-1 cells.Compared with single drug group,the combination of these two drugs could significantly inhibit the proliferation of breast cancer and prolong the survival time of mice with triple negative breast cancer.Conclusions The combined application of pargyline and doxorubicin has a synergistic inhibitory effect on the proliferation,migration and invasion of mouse breast cancer 4T-1 cells,and has potential value for clinical treatment on triple-negative breast cancer.