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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。
Objective: To investigate the inhibitory effect of arsenic trioxide (AS2O3) combined with all-trans retinoic acid (ATRA) on human ovarian carcinoma cell line SKOV3 and its mechanism. Methods MTT assay, flow cytometry and immunofluorescence were used to detect the effects of AS2O3 alone and in combination with ATRA on the proliferation and apoptosis of ovarian cancer cells . RESULTS: ATRA alone had no effect on the growth of SKOV3 cells. AS2O3 alone could inhibit the growth of SKOV3 cells. Combination of AS2O3 and ATRA was more effective than AS2O3 alone in SKOV3 cells (P <0.05). Flow cytometry confirmed (P <0.05). The apoptosis of SKOV3 cells increased at G2 / M phase and decreased at S phase (P <0.05) after 5.0μmol / L AS2O3 combined with 1.0μmol / L ATRA for 48h. Necrotic cells decreased (P <0.05). CONCLUSION: AS2O3 can up-regulate the expression of cell cycle arrest protein P27 in SKOV3 cells. ATRA combined with AS2O3 can enhance the above effects. Therefore, ATRA sensitizes SKOV3 cells to apoptosis, which may depend on overexpression of P27, a negative regulator of cell cycle.