蛇床子素对鼻咽癌裸鼠移植瘤放疗作用的影响及作用机制  

Effect of osthole on radiotherapy of transplanted human nasopharyngeal carcinoma in nude mice and relevant mechanism

作　　者：陈炯玉[1] 庄轶轩[1] 陈鑑 彭琳[1] CHEN Jiong-yu;ZHUANG Yi-xuan;CHEN Jian;PENG Lin(Central Laboratory, Cancer Hospital of Medical College, Shantou University, hantou 515041, Guangdong Province, China)

机构地区：[1]汕头大学医学院附属肿瘤医院,广东汕头515041

出　　处：《中国生物制品学杂志》2018年第5期479-484,共6页Chinese Journal of Biologicals

基　　金：国家自然科学基金青年基金(81602886);广东省自然科学基金(2016A030313062);广东省医学科研基金(B2018222);汕头市科技计划项目([2015]113)

摘　　要：目的探讨蛇床子素(osthole)对鼻咽癌裸鼠移植瘤放疗作用的影响及其可能的机制。方法将鼻咽癌CNE2细胞株经NU/NU裸鼠右腋皮下接种,2×10~8个/只,待移植瘤长至150mm^3时,随机分为对照组(隔1 d经腹腔注射无菌生理盐水,0.2 m L/只)、单纯蛇床子素组[隔1 d经腹腔注射,1.5μg/(g·10μL)]、单纯放疗组(5 Gy/次,隔3 d X射线照射1次)、蛇床子素联合放疗组(经腹腔注射蛇床子素2 h后进行放射治疗,剂量与方法同单纯蛇床子素组及单纯放射组)。每3 d测量移植瘤体积,首次给药后第21天取出移植瘤,称瘤重;流式细胞术检测移植瘤细胞凋亡率;荧光定量PCR及Western blot法分别检测移植瘤细胞中血管内皮生长因子(vascular endothelial growth factor,VEGF)及乏氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)基因m RNA转录和蛋白表达水平。结果与对照组比较,单纯蛇床子素组、单纯放疗组及蛇床子素联合放射组裸鼠移植瘤体积及瘤重均明显下降(P<0.05),细胞凋亡率明显升高(P<0.05),其中蛇床子素联合放射组最显著,且该组裸鼠移植瘤中VEGF及HIF-1α基因m RNA转录及蛋白表达水平明显低于单纯蛇床子素组及单纯放疗组(P<0.05)。结论蛇床子素可增强鼻咽癌裸鼠移植瘤对放疗的敏感性,其机制可能与下调VEGF及HIF-1α表达,抑制血管生成有关。Objective To investigate the effect of osthole on therapy of transplanted nasopharyngeal carcinoma（NPC） in nude mice as well as the possible mechanisms. Methods CNE2 cells were inoculated s. c. to 20 NU/NU nude mice in the right axillas,2 × 10-8 cells for each. When the tumor size reached 150 mm-3,the mice were randomly divided into control, osthole,radiotherapy and osthole ＋ radiotherapy groups. The mice in control group were injected i. p. with0. 2 m L of physiological saline every other day,while those in osthole group with 1. 5 μg/（g·10 μL）osthole,and those in radiotherapy received radiation with X-ray at a dosage of 5 Gy every 3 d. However,the mice in osthole ＋ radiotherapy group received radiation at the same dosage 2 h after injection i.p. with 1. 5 μg/（g·10 μL） osthole. The tumor size was measured every 3 d,while the tumors were taken out and weighed 21 d after the first injection. The apoptosis rate of CNE2 cells was determined by flow cytometry,while the m RNA transcription and protein expression levels of vascular endothelial growth factor（VEGF）and hypoxia inducible factor-1α（HIF-1α）by fluorescent quantitative PCR and Western blot. Results Both size and weight of tumors in osthole,radiotherapy and osthole ＋ radiotherapy groups,especially in osthole ＋ radiotherapy group,decreased significantly,while the cell apoptosis rate increased significantly,as compared with those in control group（each P〈0. 05）. However,both the m RNA transcription and protein expression levels of VEGF and HIF-1α in osthole ＋ radiotherapy were significantly lower than those in osthole and radiotherapy groups（each P〈0. 05）. Conclusion Osthole may increase the sensitivity of NPC in nude mice to radiotherapy by a possible mechanism of down-regulation of expressions of VEGF and HIF-1α and inhibition of angiogenesis.

关 键 词：蛇床子素 鼻咽癌 裸鼠 放疗 血管内皮生长因子 乏氧诱导因子-1Α 

分 类 号：R739.62[医药卫生—肿瘤] R73-3621[医药卫生—临床医学]