目的：探讨microRNA-129-2（miR-129-2）对人鼻咽癌CNE1细胞裸鼠移植瘤生长的抑制作用及其可能的机制。方法：建立人鼻咽癌CNE1细胞裸鼠皮下移植瘤模型，按皮下注射的药剂将32只模型小鼠用随机数字表法分为4组：对照组（皮下注射生理盐水0.2 ml/d）、空白质粒组\[(50 μg/只,0.2 ml/次，1次/d\]、顺铂（cisplatin，DDP）阳性对照组(1 mg/kg, 0.2 ml/次，1次/d）、miR-129-2组\[(50 μg/只,0.2 ml/次，1次/d\]，共治疗5周，记录裸鼠体质量、肿瘤体积、肿瘤质量。流式细胞术检测各组移植瘤组织S+G2-M期细胞比例，免疫组化和Western blotting方法检测miR-129-2对移植瘤组织中转录因子SOX4表达的影响。结果：成功建立CNE1细胞裸鼠皮下移植瘤模型，治疗第22天起，miR-129-2组移植瘤的体积和质量均显著低于对照组和空白质粒组（P<0.01），而与DDP组始终无明显差异（P>0.05）；5周后，miR-129-2组荷瘤小鼠的体质量显著高于其他3组（均P<001）。miR-129-2组移植瘤组织S+G2-M期细胞比例显著低于与对照组和空白质粒组（P<0.01），与DDP组无显著差异（P>0.05）。移植瘤组织SOX4表达显著高于瘤旁组织， miR-129-2组和DDP组移植瘤组织内SOX4蛋白表达均较对照组显著降低（均P<0.01），且miR-129-2组SOX4蛋白表达显著低于DDP组 （P<0.05）。结论： miR-129-2对人鼻咽癌CNE1细胞裸鼠皮下裸移植瘤的生长有明显的抑制作用，其机制可能与SOX4表达下调有关。

Objective: To investigate the inhibitory effect of microRNA-129-2(miR-129-2) on xenografted human nasopharyngeal carcinoma development and SRY-related HMG-box transcription factor (SOX4) expression in nude mice. Methods: Nude mice were injected with human nasopharyngeal carcinoma CNE1 cells. Animals with confirmed tumor lesions were randomized into 4 treatment groups (n=8): saline control (subcutaneous injection of saline 0.2 ml/d), blank plasmid control (50 μg each mice in 0.2 ml daily), cisplatin (DDP) (1 mg/kg in 0.2 ml daily ) and miR-129-2 (50 μg each mice in 0.2 ml daily). At 5 weeks after treatment, body weight and tumor volume and weight were measured, the proportion of cells at S/G2-M arrest in xenografted tumor cells was assessed by flow cytometry, and SOX4 protein content in xenograft tumors was assessed by immunohistochemical analysis and Western blotting. Results: In nude mice that developed nasopharyngeal carcinoma lesions after grafting of CNE1 cells, miR-129-2 led a significant decrease, comparable to that resulted from DDP treatment, in tumor volume and weight (P<0.01) whereas the control plasmid showed no effect (P>005), as compared with the non-treatment control 22 days after treatment. Mice in the miR-129-2 group were significantly heavier than all other three groups of animals (P<0.01). The proportion of cells at S/G2-M arrest was (37.95±151)% in the non-treatment group, which was not different from the control plasmid group (36.75±1.48)% but significantly decreased (P<0.01) in the miR-129-2 group (31.81±1.45)% and the DDP treatment group (32.34±1.67)%. SOX4 protein content was significantly higher in tumors than in peritumoral tissues (P<0.05). Both miR-129-2 and DDP significantly lowered SOX4 protein content in tumors (P<0.01), but the effect of miR-129-2 was more pronounced. Conclusion: The small non-coding RNA molecule miR-129-2 is capable of suppressing the growth of xenografted human nasopharyngeal carcinoma through down-regulation of SOX4 expression in nude mice, thus possessing a therapeutic potential for nasopharyngeal carcinoma.

国家自然科学基金资助项目（No. 81373403），广西硕士研究生科研创新资助项目（No. YCSZ2013031），广西卫生厅课题资助项目（No. Z202066），广西医科大学青年基金课题资助（No. 02604001020）。