5种药物对乳腺癌细胞分化和增殖抑制作用的比较

Effects of Five Different Drugs on Differentiation Induction and Proliferation Inhibition of Breast Cancer Cell Line

[目的]探讨全反式维甲酸(ATRA)、1α,25-二羟维生素D3、盐酸强力霉素、雷洛芬和硫链丝菌肽对乳腺癌细胞MCF-7分化诱导、细胞微环境、细胞增殖影响的差异。[方法]油红O染色检测上述5种药物对MCF-7细胞分化诱导作用;台盼蓝染色检测上述5种药物对MCF-7细胞增殖的抑制作用。[结果 ]5种药物对MCF-7均有很强的分化诱导作用,且呈剂量依赖性。在0.08μmol/L时雷洛芬的分化诱导作用最强,盐酸强力霉素、硫链丝菌肽、1α,25-二羟维生素D3次之。诱导形成的小脂肪滴经油红O染色,显示相似颜色,但高浓度药物诱导形成的大脂肪块染色后,显示颜色的差异,ATRA诱导形成的大脂肪块染色后显示鲜红色,其他4种药物诱导形成的大脂肪块显示较暗的紫红色。脂肪块或脂肪滴主要位于细胞间质,少部分位于胞浆。硫链丝菌肽对MCF-7增殖的抑制作用远强于其他4种药物。[结论]5种药物均可诱导MCF-7细胞分化,改变细胞微环境。在0.08μmol/L时,雷洛芬的分化诱导率最高,盐酸强力霉素、硫链丝菌肽、1α,25-二羟维生素D3次之。它们所形成的脂肪滴成分可能相似,但有所差异。硫链丝菌肽对MCF-7增殖的抑制作用远强于其他4种药物。

[Objective] To investigate the effects of different drugs on differentiation induction and proliferation inhibition of breast cancer MCF-7 cells. [Methods] Human breast cancer MCF-7cells were treated with ATRA,calcitriol,doxycycline,raloxifene or thiostrepton in vitro,respectively. The differentiation induction of MCF-7 cells was detected by Oil Red O staining. The cell proliferation was measured by trypan blue assay. [Results] The differentiation of MCF-7 was induced by all 5 drugs in a dose-dependent manner. Among 5 different drugs,raloxifene was the most effective inducer at 0.08μmol/L,followed by doxycycline,thiostrepton and calcitriol. The induced lipid droplets showed similar color after Oil Red O staining. However,the lipid chunks accumulated by small lipid droplets induced by the above 5 different drugs at high concentrations showed different coloring after Oil Red O staining： the lipid chunks,induced by ATRA appeared to be bright red and the ones induced by other 4 drugs were dark purple. The lipid chunks or droplets were mainly located in the extracellular matrix,with few in cytoplasm. The proliferation inhibition of MCF-7 cells by thiostrepton was much stronger than that by other 4 drugs in a dosedependent manner. [Conclusion] ATRA,calcitriol,doxycycline,raloxifene or thiostrepton can induce the differentiation of breast cancer MCF-7 cells with various degrees. Among 5 drugs,thiostrepton has the strongest effect on the proliferation inhibition of MCF-7 cells.