丹酚酸B对人鼻咽癌裸鼠移植瘤模型的放疗增敏效应

Salvianolic Acid B Enhances Radiosensitivity of Nasopharyngeal Carcinoma Xenografts in Nude Mice

目的探讨丹酚酸B（salvianolic acid B）对人鼻咽癌裸鼠移植瘤模型的放疗增敏作用及可能的机制。方法将人鼻咽癌CNE2细胞株接种于20只4-6周龄BALA/c裸鼠皮下,肿瘤长至4-6mm时随机分为4组,分别为对照组、丹酚酸B组[20mg/（kg·d）]、放疗组（20Gy）、丹酚酸B[20mg/（kg·d）]联合放疗组。各组裸鼠给予相应的处理措施,定期测量瘤体体积,4周后处死裸鼠,剥离瘤体称重,分别计算各组抑瘤率。采用流式细胞仪检测各组瘤体肿瘤细胞凋亡率;采用荧光定量PCR检测瘤体组织中HIF-1α、VEGF mRNA表达水平,采用Western blot检测瘤体组织中HIF-1α、VEGF蛋白表达水平。结果丹酚酸B联合放疗组裸鼠移植瘤的体积和重量显著下降,相比对照组、丹酚酸B及放疗组差异均具有统计学意义（均P〈0.05）;丹酚酸B联合放疗组瘤体肿瘤细胞凋亡率显著增加,相比对照组、丹酚酸B及放疗组差异均具有统计学意义（均P〈0.05）;丹酚酸B联合放疗组HIF-1α、VEGF mRNA及蛋白表达水平显著下降,与其他各组相比,差异均具有统计学意义（均P〈0.05）。结论丹酚酸B能增强鼻咽癌裸鼠移植瘤对放疗的敏感性,其作用机制可能与降低HIF-1α、VEGF的表达,从而抑制肿瘤血管生成相关。

Objective To investigate the role of salvianolic acid B in the radiosensitivity of nasopharyngeal carcinoma xenografts in nude mice.Methods CNE2 cells（a human nasopharyngeal cell line）were inoculated into 4-6week old BALA/c nude mice.When the xenografts grew to 4-6cm,nude mice（n=20）were randomly divided into 4 groups：normal control（NC）group,salvianolic acid B[20mg/（kg·d）]group,radiotherapy（20Gy）group,salvianolic acid B[20mg/（kg·d）]plus radiotherapy（20Gy）group.After 4-week treatment,the tumor volume and weight were obtained,and the tumor inhibition rate was calculated.Flow cytometry was used to detect the apoptosis rate of tumors,real-time PCR to detect the expression of HIF-1α and VEGF mRNA in tumors,and Western blotting to measure the expression of HIF-1α and VEGF protein in tumors.Results The volume and weight of the xenograft tumors were significantly decreased and the apoptosis rate of the xenograft tumors was obviously increased in salvianolic acid B plus radiotherapy group as compared with those in NC group,salvianolic acid B group and radiotherapy group（P〈0.05 for all）.The mRNA and protein expression levels of HIF-1α and VEGF were significantly lower in salvianolic acid B plus radiotherapy group than in other groups（P〈0.05）.Conclusion Salvianolic acid B can enhance the sensitivity of radiotherapy to the nasopharyngeal carcinoma xenografts in nude mice and the mechanisms may involve the suppression of HIF-1α and VEGF expression and thereby the tumor angiogenesis.