摘要
目的:观察甲基硒酸(methylseleninic acid,MSA)对人三阴性乳腺癌细胞的化疗增敏作用及其机制。方法:采用MSA联合紫杉醇、阿霉素与三阴性乳腺癌MDA-MB-231细胞株共培养,分别应用CCK-8实验检测化疗药物单药和联合MSA用药时细胞增殖抑制率,并通过计算合用指数,探讨MSA对化疗药物疗效的影响;用流式细胞术检测细胞周期的分布情况;应用Annexin V-FITC/PI双染法检测细胞凋亡变化。结果:不同浓度化疗药物联合MSA后细胞增殖率较单用化疗药物组均下降,呈明显的量-效关系,提示MSA与化疗药物具协同作用;紫杉醇联合MSA时G2/M期细胞较单药明显增多(P<0.05),阿霉素联合MSA时S期细胞较单药明显增多(P<0.05),提示MSA增强了抗肿瘤药物诱导的肿瘤细胞周期阻滞效应;与单用同一浓度的同一化疗药物相比,10nmol/L紫杉醇联合3.5μmol/L MSA后细胞凋亡率由41.1%上升至59.3%(P<0.05),0.5μmol/L阿霉素联合3.5μmol/L MSA后细胞凋亡率由30.2%上升至51.9%(P<0.01),提示MSA增强了抗肿瘤药物诱导肿瘤细胞凋亡的效应。结论:MSA能增强化疗药物阿霉素和紫杉醇对三阴乳腺癌细胞的抗肿瘤效果,其机制之一可能是增强了抗肿瘤药物诱导的肿瘤细胞凋亡和周期阻滞效应。
AIM ： To observe the chemosensitization effect of methylseleninic acid （MSA） on human triplenegative breast cancer （TNBC） cells. METHODS： MDA-MB-231 cell line was co-cultured with MSA plus paclitaxel or doxorubicin. The inhibitory rate of cell proliferation was detected by CCK-8 assay. The combination index was calculated to explore the impact of MSA on the efficacy of chemotherapeutic drugs. The cell cycle was analyzed by flow cytometry. Annexin V-FITC/PI double staining was applied to detect the cell apoptosis. RESULTS ： Compared with single usage of chemotherapeutic drugs, the cell proliferation rates were decreased when the chemotherapeutic drugs was combined with MSA, suggesting that there is a synergistic relationship between MSA and chemotherapeutic drugs. Compared with the single-agent groups, the G2/M-phase cells in paclitaxel combined with MSA group increased significantly （P 〈0. 05） ,and the S-phase cells increased significantly in doxorubicin combined with MSA group （P 〈 0. 05）. These suggested that MSA enhanced the anticancer effect of the drugs by inducing cell cycle arrest. Compared with single usage of 10 nmol/L paclitaxel, the apoptotic rate increased from 41.1% to 59.3% （P 〈0. 05） as 10 nmol/L paclitaxel combined with 3.5 μmol/L MSA was used. Compared with single usage of 0.5 μmol/L doxorubicin, the apoptotic rate increased from 30.2% to 51.9% （P 〈 0.01 ） as 0.5 μmol/L doxorubicin combined with 3.5 μmol/L MSA was used. These suggested that MSA enhanced antitumor effect of the drugs by inducing tumor cell apeptosis. CONCLUSION： MSA enhances the antitumor effects of chemotherapeutic drugs doxorubicin and paclitaxel on TNBC cells. One of the possible mechanisms is the enhancement of indu-cing tumor cell apoptosis and cell cycle arrest.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2013年第11期1990-1993,共4页
Chinese Journal of Pathophysiology
基金
广东省科技计划(No.2008B030301128)
关键词
甲基硒酸
三阴性乳腺癌
化疗增敏
细胞周期阻滞
细胞凋亡
Methylseleninic acid
Triple-negative breast cancer
Chemosensitization
Cell cycle arrest
Apoptosis
