18F-FDG对小鼠Lewis肺癌移植瘤P53、XIAP与GADD45蛋白表达的影响  

Effects of 18F-FDG on P53, XIAP, and GADD45 expressions in transplanted Lewis lung carcinoma in mice

作　　者：程义壮[1] 姚晓波[1] 吴翠萍[2] 王永生[2] 陈柯[1] 张伍魁[2] 王明明[2] 

机构地区：[1]安徽省立医院核医学科,合肥230001 [2]安徽医科大学临床医学院放射医学研究所

出　　处：《中华放射医学与防护杂志》2014年第12期884-888,共5页Chinese Journal of Radiological Medicine and Protection

基　　金：国家自然科学基金（81273003）;安徽省自然科学基金（1208085MH162）;安徽省科技攻关项目（10021303035）;安徽省教育厅自然科学基金（KJ2011Z162）

摘　　要：目的 观察18F-氟代脱氧葡萄糖（18F-FDG）内照射对Lewis肺癌移植瘤P53、XIAP与GADD45蛋白表达的影响,探讨其作为内照射治疗药的可行性.方法 建立Lewis肺癌C57BL/6小鼠皮下移植瘤模型48只,随机数字表法分为高剂量组、低剂量组和对照组,每组16只.接种后第7天,3组小鼠分别腹腔注射0.2 ml 18F-FDG及等体积生理盐水,使高、低剂量组18F-FDG注射量分别为18.5×107和9.25×107 Bq.第22天处死小鼠,SP免疫组织化学法检测移植瘤组织P53、XIAP与GADD45蛋白表达.结果 每种蛋白3组小鼠间表达差异有统计学意义（x2=8.30、16.02、7.68,P ＜0.05）.3组小鼠Lewis肺癌P53蛋白表达的平均积分光密度分别从对照组的（0.089±0.033）随照射剂量增大为高剂量组的（0.315±0.028）;XIAP蛋白表达的平均积分光密度从（0.422±0.034）逐步减小为（0.149±0.055）;GADD45蛋白表达的平均积分光密度从（0.126±0.023）逐步上升为（0.383±0.035）.3组间蛋白表达量差异有统计学意义（P53：F =5.26,P＜0.05;XIAP：F=4.29,P＜0.05;GADD45：F=5.98,P＜0.05）.结论 18F-FDG能够上调P53和GADD45蛋白表达,下调XIAP蛋白表达,促使小鼠Lewis肺癌组织细胞以P53依赖的方式凋亡,抑制Lewis肺癌移植瘤生长.Objective To study the effects of internal exposure of 18F-FDG （18F-2-deoxy-2-fiuoroD-glucose） on the protein expressions of P53,XIAP （X-linked inhibitors of apoptosis protein） and GADD （growth arrest and DNA damage）45 in Lewis lung carcinoma,and to explore the possibility of applying 18F-FDG as a radiotherapy drug in vivo.Methods Lewis lung cancer transplanted tumor models were established via subcutaneous injection of 0.2 ml of 2 × 107/ml Lewis lung carcinoma cells at left hind limbs of 48 C57BL/6 mice that were randomly divided into high dose group,low dose group and control group with 16 mice each.After 7 d of cancer cell inoculation,18.5 × 107 Bq and 9.25 × 107 Bq of 18F-FDG in 0.2 ml saline or equal volume of physiological saline was intraperitoneally injected into three group mice,respectively.22 d post inoculation,the protein expressions of P53,XIAP and GADD45 were immuohistochemically detected by using SP approach.Results There was significant difference among the protein expressions in each group （x2 =8.30,16.02,7.68,P 〈0.05）.The mean integral optic density of protein expression increased from 0.089 ± 0.033 in control group to 0.315 ± 0.028 in high dose group for P53,and from 0.126 ± 0.023 to 0.383 ±-0.035 for GADD45,but it decreased from 0.422 ± 0.034 to 0.149 ± 0.055 for XIAP.There was significantly difference of these protein expressions in each group （P53：F=5.26,P〈0.05;XIAP：F=4.29,P 〈0.05;GADD45：F=5.98,P 〈0.05）.Conclusions 18F-FDG can up-regulate the expressions of P53 and GADD45 proteins and down-regulate the expression of XIAP protein in tumor cells,and it inhibits tumor growth by promoting cell apoptosis in the Lewis lung carcinoma tissue with a P53-dependent manner.

关 键 词：LEWIS肺癌 P53蛋白 XIAP蛋白 GADD45蛋白 

分 类 号：R734.2[医药卫生—肿瘤]