亚砷酸对裸鼠宫颈癌移植瘤模型的干预研究

Anti-Tumor Effect of Arsenious Acid on Cervical Cancer Xenografts in Nude Mice

目的建立宫颈癌移植瘤模型,研究亚砷酸的体内干预效果及机制。方法将Hela细胞注射于裸鼠皮下接种,成瘤后腹腔分别连续注射亚砷酸、卡铂及生理盐水14 d,观察肿瘤大小和裸鼠精神状态,用流式细胞术(FCM)检测细胞凋亡和细胞周期。结果亚砷酸组小鼠精神状态良好。与对照组比较,亚砷酸组治疗7 d后肿瘤生长速度减慢;治疗14 d肿瘤重量显著性降低(P<0.05),抑瘤率达到35.8%,高于卡铂组的27.9%;治疗14 d肿瘤细胞的凋亡率显著升高(P<0.01),增殖指数(PI)显著降低(P<0.01),处于G0/G1周期的细胞明显增多(P<0.01),处于G2/M周期的细胞明显减少(P<0.05)。结论亚砷酸具有抑制宫颈癌移植瘤生长的作用,且未见明显毒副作用,其抑瘤的机理可能与诱导肿瘤细胞凋亡、干扰肿瘤细胞生长周期和抑制肿瘤细胞增殖有关。

Objective To establish a mouse model of cervical cancer, to study the effect of arsenious acid on the tumor growth in vivo, and the mechanism of intervention. Methods HeLa cells were subcutaneously injected into female nude mice. Arsenious acid, carboplatin and saline were injected intraperitoneally after tumor inoculation for 14 days continuously, respectively. The changes of tumor size and general condition of nude mice were recorded. Cell apoptosis and cell cycle were detected by flow cytometry （FCM）. Results The mice of the arsenious acid group showed a good state of health. Compared with the control group, the tumor growth of arsenious acid group slowed down after the seventh day （P 〈 0.05）, and the tumor weight decreased significantly on the fourteenth day （ P 〈 0.05）, with an inhibition rate of 35.8 %, higher than 27.9 % of the carboplatin group. The apoptosis rate of tumor cells of the arsenious acid group significantly increased （P 〈 0.01 ）, the proliferation index （P I） significantly lower （P 〈 O. O1 ）, the cells at G0/G1 phases increased significantly （P 〈 0.01 ）, and the cells at G2/M cell phase decreased significantly （ P 〈 0.05）. Conclusions Arsenious acid can inhibit the proliferation of tumor and there is no apparent side effect to the nude mice under the conditions used in this study. The inhibiting mechanism of arsenious acid on cervical cancer may be related to induction of tumor cell apoptosis, interference of tumor cell cycle, and inhibiting the proliferation of tumor cells.