亚砷酸联合顺铂对鼻咽癌裸鼠移植瘤生长和p16基因甲基化的作用

发布时间：2018-05-21 18:23

本文选题：鼻咽癌 + p　；参考：《广东医学》2014年07期

【摘要】：目的探讨p16异常甲基化与鼻咽癌间的相关性及亚砷酸联合顺铂抑制鼻咽癌裸鼠移植瘤恶性表型和逆转甲基化状态的作用及机制。方法建立人鼻咽癌CNE-2Z细胞裸鼠移植瘤模型,随机分为空白对照(Control)组、亚砷酸(As2O3)组、顺铂(DDP)组及联合(As2O3+DDP)组。(1)Control组:生理盐水0.2 mL/次,腹腔注射1次/d,共14次;(2)As2O3组:As2O35 mg/kg,腹腔注射1次/d,共14次。(3)DDP组:DDP 3 mg/kg,每隔2天腹腔注射1次,共4次。(4)As2O3+DDP组:As2O35 mg/kg,腹腔注射1次/d,共14次;DDP 3 mg/kg,每隔2天腹腔注射1次,共4次。停药后次日处死裸鼠,取出移植瘤。光镜下观察各组移植瘤组织细胞病理形态学变化,采用HRM法检测各组移植瘤p16启动子区甲基化率;采用Real-time RT-PCR法检测各组移植瘤p16 mRNA表达;采用免疫组化SP法检测各组移植瘤p16蛋白表达。结果 As2O3、DDP、As2O3+DDP均能抑制人鼻咽癌CNE-2Z裸鼠移植瘤生长,与Control组比较,各用药组裸鼠移植瘤体积较小(P0.05),瘤重较轻(P0.05);与Control组比较,As2O3组p16甲基化率略低(P0.05),DDP组、As2O3+DDP组p16甲基化率明显降低(P0.05),与DDP组比较,As2O3+DDP组移植瘤p16甲基化率明显降低(P0.05);各用药组p16基因mRNA和蛋白表达量较高(P0.05),差异均有统计学意义,且As2O3+DDP明显优于As2O3、DDP单一用药(P0.05)。结论 As2O3、DDP、As2O3+DDP均可抑制鼻咽癌细胞恶性表型和逆转p16甲基化状态。
[Abstract]:Objective to investigate the relationship between p16 aberrant methylation and nasopharyngeal carcinoma (NPC), and to investigate the role and mechanism of arsenite combined with cisplatin in inhibiting malignant phenotype and reversing methylation of transplanted nasopharyngeal carcinoma (NPC) in nude mice. Methods the transplanted tumor model of human nasopharyngeal carcinoma (NPC) CNE-2Z cells in nude mice was established and randomly divided into three groups: control group, As2O3 group, DDP group and control group: normal saline 0.2 mL/. Once a day, 14 times as _ 2O _ 3: 35 mg / kg, once a day, 14 times a day, a total of 14 times: DDP: 3 mg / kg, once every 2 days, 4 times a day, 4 times, 4 times: as _ 2O _ 3: as _ 2O _ 3 mg / kg, intraperitoneal injection of 1 / d, 14 times DDP _ 3 mg / kg, once every 2 days, 4 times. The next day after withdrawal, nude mice were killed and transplanted tumors were removed. The histopathologic changes of xenografts in each group were observed under light microscope, the methylation rate of p16 promoter was detected by HRM method, the expression of p16 mRNA was detected by Real-time RT-PCR method. Immunohistochemical SP method was used to detect the expression of p16 protein. Results as _ 2O _ 3 DDP _ 2O _ 3 DDP could inhibit the growth of human nasopharyngeal carcinoma (NPC) CNE-2Z xenografts in nude mice, compared with Control group. Compared with Control group, the p16 methylation rate of as 2O 3 group was slightly lower than that of Control group. The p16 methylation rate of as 2O 3 DDP group was significantly lower than that of DDP group, and the p16 methylation rate of as 2O 3 DDP group was significantly lower than that of DDP group. The expression of p16 gene mRNA and protein in the drug group was higher than that in the control group (P 0.05). As2O3 DDP was better than as _ 2O _ 3 DDP alone (P 0.05). Conclusion as _ 2O _ 3 DDP _ 2O _ 3 DDP can inhibit malignant phenotype and reverse p16 methylation of nasopharyngeal carcinoma cells.
【作者单位】：广东医学院附属医院耳鼻咽喉科;广东医学院生物化学与分子生物学研究所;
【基金】：广东省湛江市科技攻关计划项目(编号:2011C3109010) 广东医学院青年基金资助项目(编号:Q2010020)
【分类号】：R739.63

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