维生素C对AS2O3抑制肺癌A549细胞增殖、诱导细胞凋亡作用的影响及机制

目的探讨维生素C对三氧化二砷（AS2O3）抗癌作用的影响及其可能机制。方法将体外培养的肺腺癌A549细胞随机分为6组，其中对照组不行特殊处理，AS2O3 1—3组分别加入0．4、4．0、40μg/ml的AS2O3，维生素C组加入400μg／ml的维生素C，联合组加入400μg／ml维生素C＋0．4μg／ml AS2O3。采用缩胆囊素八肽（CCK-8）法及克隆形成实验检测细胞生长情况（A值），用流式细胞仪检测细胞周期及凋亡率，用RT-PCR方法检测Caspase-3 mRNA、多药耐药相关蛋白基因1（MRP1）mRNA、多药耐药基因1（MDR1）mRNA表达情况（维生素C组）。结果联合组及AS2O3 2、3组A值均显著低于对照组及AS：O3组、维生素C组，且随作用时间延长逐渐降低（P〈0．05）；联合组细胞集落显著少于其他五组，G0／G1期所占比例及凋亡率均显著高于其他五组（P〈0．05）；维生素C组Caspase-3 mRNA、MDR1 mRNA表达升高（P〈0．05）、MRP1 mRNA表达无明显变化（P〉0．05）。结论维生素C对As2O3抗肺腺癌A549细胞的作用具有协同性，可能机制为上调Caspase-3表达；两者联用可望成为低毒高效的化疗组合。

Effect of Vitamin C on the arsenic trioxide roles of inhibiting the proliferation and inducing the apoptosis in lung carcinoma cell lines A549 and its mechanism

Objective To investigate the effect of Vitamin C on the anti-cancer roles of arsenic trioxide （AS2O3 ） and the possible mechanism. Methods A549 cells cultured in vitro were divided into 6 groups randomly. The control gruop was given no especial treatment, and AS2O3 1-3 group were treated with AS2O3 at the concentration of 0.4,4.0,40 μg/ml, the Vitamin C gruop was treated with Vitamin C of 400 μg/ml,the combined group was treated with Vitamin C of 400 μg/ml ＋ 0.40 μg/ml AS203-The cell proliferation （A value）was measured by CCK-8 assay and clonogcntic assay, the ceil cycle and apoptosis were detected by flow cytometry, the expressions of Caspase-3 mRNA, MRPI mRNA, MDR1 mRNA were measured by RT-PCR assay（Vitamin C group）. Results The absorbance of the combined group and AS2O3 2-3 groups were significantly lower than that of the AS2O3 1 group and Vitamin C group,which decreased gradually with the time extension （P 〈 0.05）. The ceil colony of the combined group was significantly fewer than that of the other groups, while the percentage of Go/Gt and apoptosis were significantly higher（ P 〈 0.05 ）. The expression of Caspase-3 mRNA and MDR1 mRNA of the Vitamin C group increased（P 〈 0.05 ） ,the expression of MRP1 mRNA showed no significant changes（ P 〉 0.05 ）. Conclusion Vitamin C has synergistic action on the antilung adenocarcinoma roles of AS2O3 , possible mechanism is related to the up-ragulation of the expression of Caspase-3 mRNA. Application of Vitamin C and AS2O3 might be a chemotherapy combination with low toxicity and efficient.