摘要
目的:观察组蛋白去乙酰化酶抑制剂(HDACIs)丁酸钠(NaB)及曲妥珠单抗Trastuzumab对人乳腺癌细胞株SKBR3细胞增殖、细胞周期及细胞凋亡的影响,探讨NaB及Trastuzumab调控乳腺癌细胞增殖的分子机制。方法:乳腺癌SKBR3细胞经NaB、Trastuzumab单独或联合作用后,MTT法检测细胞增殖情况,流式细胞仪分析细胞周期分布及细胞凋亡,Western Blot方法检测p27Kip1的表达。结果:NaB单独用药显著抑制SKBR3细胞增殖,促进细胞G0/G1期阻滞,增加细胞凋亡和p27Kip1蛋白的表达,P<0.05;20μg/mL Trastuzumab单独用药,对细胞有增殖抑制和细胞周期阻滞作用(P<0.05),但对细胞凋亡及p27Kip1蛋白表达无明显影响,P>0.05。Trastuzumab可协助NaB增加对SKBR3的抗肿瘤作用及p27Kip1蛋白表达,P<0.05。结论:Trastuzumab联合NaB抑制乳腺癌细胞的增殖,促进细胞周期阻滞及细胞凋亡的发生,以上过程可能是通过增加p27Kip1的蛋白表达来实现。
OBJECTIVE：To study the effect and mechanism of histone deacetylase inhibitors sodium butyrate （NaB） and the humanized antibody Trastuzumab upon the proliferation,cell cycle and apoptosis of SKBR3 breast cancer cell line.METHODS：SKBR3 cells were treated with NaB,Trastuzumab and NaB plus Trastuzumab.Cell proliferation was determined by MTT assay,cell cycle and apoptosis were assayed by flow cytometry.The expression of p27Kip1 was detected by Western Blot.RESULTS：NaB treatment significantly inhibited the proliferation of SKBR3 cells,and induced cell cycle arrest at G0/G1 and apoptosis,furthermore,NaB upregulated the expression of p27Kip1 in SKBR3 cells （P0.05）.However,Trastuzumab single-drug exhibit the proliferative inhibition and cell cycle arrest effect only at the concentration of 20 μg/mL（P0.05）,but had little influence on apoptosis and p27Kip1 expression （P0.05）,whereas,NaB plus Trastuzumab could enhance the anti-cancer effect of NaB and upregulate p27Kip1 expression in SKBR3 cells （P0.05）.CONCLUSION：Trastuzumab and NaB can synergistically inhibit the proliferation of SKBR3 breast cancer cell line,induce cell cycle G0/G1 arrest and apoptosis,which may be associated with the evaluated expression of p27Kip1.
出处
《中华肿瘤防治杂志》
CAS
2010年第20期1601-1604,共4页
Chinese Journal of Cancer Prevention and Treatment
基金
国家自然科学基金(30870962
30470669)
南京军区南京总医院课题(2009M013)
关键词
乳腺肿瘤
丁酸类/药理学
细胞增殖
breast neoplasms
butyric acids/pharmacology
cell proliferation
