甲基硒酸对紫杉醇治疗人三阴性乳腺癌的增敏作用

Sensitization Effect of Methylseleninic Acid in Paclitaxel Treatment of Three Negative Breast Cancer

目的探讨甲基硒酸(methylseleninic acid,MSA)对紫杉醇治疗人三阴性乳腺癌(three negative breast cancer,TNBC)细胞的化疗增敏作用。方法分别采用MSA(4.5μmol/L)、紫杉醇(40 nmol/L)处理人乳腺癌细胞系MDA-MB-231(空白对照组:MSA-紫杉醇-;紫杉醇组:MSA-紫杉醇+;MSA组:MSA+紫杉醇-;联合用药组:MSA+紫杉醇+)。观察不同时间点MDA-MB-231细胞的体外增殖、细胞周期和细胞凋亡情况。结果 MSA组、紫杉醇组、联合用药组MDA-MB-231细胞的体外增殖抑制率、G1期细胞百分比、细胞凋亡率显著高于空白对照组(P<0.05),而各用药组的S期细胞百分比显著低于空白对照组(P<0.05),且上述作用均呈时间依赖性;不同时间条件下,联合用药组的体外增殖抑制率、G1期细胞百分比、细胞凋亡率显著高于空白对照组、紫杉醇组、MSA组(P<0.05),而MCF-7细胞的S期细胞百分比显著低于其他三组(P<0.05)。结论在MSA的增敏作用下,紫杉醇通过细胞周期G1/S阻滞效应抑制了MCF-7细胞的体外增殖,并强化了细胞凋亡诱导作用,更好地发挥对人TNBC的化疗治疗作用。

Objective To investigate the chemotherapy sensitizing effect of paclitaxel combined with methylseleninic acid（MSA）in three negative breast cancer（TNBC）.Methods Breast cancer cell line MDA-MB-231 was cultured with4.5μmol/L MSA（MSA group）,40nmol/L paclitaxel（paclitaxel group）and MSA combined with paclitaxel（combination therapy group）respectively.Cells without MSA or paclitaxel treatment were control group.Changes of breast cancer cell proliferation,cell cycle,apoptosis in each group were observed.Results The inhibition rates of proliferation in vitro,the percentages of G1 phase cells and the rates of cell apoptosis in MSA group,Paclitaxel group and combination therapy group were significantly higher than the control group（P〈0.05）,while the percentages of S phase cells were significantly lower than the control group（P〈0.05）.All effects mentioned above were time dependent.At different time points,the inhibition rate of proliferation in vitro,the percentage of G1 phase cells and the rate of cell apoptosis in combination therapy group were all significantly higher than the control group（P〈0.05）,paclitaxel group and MSA group,while the percentage of S phase cells in combination therapy group was decreased significantly than other three groups（P〈0.05）.Conclusion Paclitaxel combined with MSA has better antitumor effect of TNBC,which can enhance tumor cell cycle arrest effect and induce apoptosis of tumor cells.