三氧化二砷联合全反式维甲酸对人卵巢癌细胞的抑制作用

目的:探讨三氧化二砷(AS2O3)联合全反式维甲酸(ATRA)对人浆液性卵巢癌细胞株SKOV3的抑制作用及其机制。方法;四甲基偶氮唑蓝光吸收法(MTT)、流式细胞术及免疫荧光法检测体外培养的SKOV3细胞在AS2O3单独作用及联合ATRA作用下对卵巢癌细胞生长的抑制及促凋亡作用。结果:单用ATRA对SKOV3细胞的生长无影响;单用AS2O3可以抑制SKOV3细胞的生长;联合使用AS2O3和ATRA较单用AS2O3对SKOV3细胞的抑制作用强(P<0.05);流式细胞术证实:5.0μmol/LAS2O3联合1.0μmol/LATRA作用48h时,SKOV3细胞出现G2/M期阻滞增强、S期减低(P<0.05);AnnffxinV染色检测到早期凋亡细胞增多,晚期凋亡及继发性坏死细胞减低(P<0.05)。结论:AS2O3能上调SKOV3细胞中细胞周期抑制蛋白P27的表达,ATRA联合AS2O3可以增强上述效应。故ATRA对诱导SKOV3细胞凋亡有增敏效应,该效应过程可能依赖于细胞周期负性调控因子P27蛋白的过度表达。

Inhibition of arsenic trioxide combined with atra to human ovarian cancer cell

Objective:To investigate the effects of arsenic trioxide and all-trans retinoic acid (ATRA) on ovarian cancer cell line SKOV3 and relative mechanism.Methods:Morphological changesof cells were observed and photoed by inverted microscope. Growth inhibition and cell cycles change of SKOV3 line induced by means of MTT/flow cytometry. Immunocytochemical staining was used to examine the expression of P27.Results:The inhibitive effect of arsenic trioxide (5.0 μmol/L) combined with ATRA(1.0 μmol/L) was obvious and the inhibitive degree was stronger than only arsenic trioxide. Higher concentrations of arsenic trioxide and all-trans retinoic acid up-regulated P27 .Conclusion:The inhibitive effect of arsenic trioxide combined with ATRA is more obvious than either one used separately; G2/M retardation is found by flow cytometry and the effect is enhanced in dose-dependent pattern.The apoptosis mechanism of ovarian cancer cell line SKOV3 is related with up-regulating of P27.