SN50联合5-氟尿嘧啶通过调节NF-κB信号通路抑制人胃癌裸鼠移植瘤生长的研究  

Study on growth inhibition of human gastric cancer xenografts in nude mice by SN50 combined with 5-fluorouracil regulating NF-κB signaling pathway

作　　者：刘静[1] 刘婷[1] 徐睿玲[1] 王新红[1] 刘冰熔[1] 

机构地区：[1]哈尔滨医科大学附属第二医院消化内科,黑龙江哈尔滨150086

出　　处：《胃肠病学和肝病学杂志》2016年第1期5-8,共4页Chinese Journal of Gastroenterology and Hepatology

基　　金：国家自然科学基金(30871152)

摘　　要：目的探讨NF-κB通路抑制剂SN50联合5-氟尿嘧啶(5-FU)对人胃癌裸鼠移植瘤生长的影响及机制。方法建立荧光素酶标记的人胃癌细胞株SGC7901,常规传代培养,采用对数生长期细胞建立人胃癌裸鼠皮下移植瘤模型。14 d后随机分为4组:对照组、5-FU干预组、SN50干预组、5-FU+SN50干预组。每组8只动物,共给药4周。观察并记录各组裸鼠皮下移植瘤的生长情况,游标卡尺测量瘤体长短径,于停药次日处死裸鼠,称取瘤重,计算肿瘤体积、肿瘤生长抑制率、绘制肿瘤生长曲线。通过体内可见光成像技术分别于第1、7、14、21、28天对裸鼠进行活体成像,记录移植瘤光子数,绘制皮下移植瘤光子数曲线图。免疫组化方法检测移植瘤中NF-κBp65表达情况。结果与其他三组相比,5-FU+SN50干预组肿瘤体积、抑瘤率及光子数差异均有统计学意义(P<0.05);与对照组及SN50干预组比较,5-FU干预组肿瘤体积和光子数明显减少(P<0.05),抑瘤率明显增加(P<0.05);SN50干预组与对照组相比,肿瘤体积、抑瘤率及光子数差异无统计学意义(P>0.05)。NF-κBp65阳性率依次为对照组47.4%、5-FU组57.1%、SN50组11.8%、5-FU+SN50组25.0%。结论 5-FU单药及5-FU+SN50均能抑制裸鼠胃癌皮下移植瘤的生长,而联合应用效果更明显;SN50可通过抑制NF-κB信号转导通路的活化,显著增强5-FU对裸鼠胃癌皮下移植瘤的抑制作用。Objective To investigate the growth inhibition of human gastric cancer xenografis in nude mice by SN50 combined with 5-fluorouracil （5-FU）. Methods Human gastric cancer SGC7901 cell line was constructed to express firely luciferase, which was conventional serial subcuhured. The models of human gastric cancer xenografts in nude mice were established, then randomly divided into 4 groups after 14 days as follows ： control group, 5-FU group, SN50 group, 5-FU ＋ SN50 group, the drugs mentioned above were administrated for 4 weeks. Bioluminescence imaging technique was applied at 1, 7, 14, 21, 28 days to nude mice. The xenograft tumor photon numbers were measured and subcutaneously transplanted tumor photon number curve was drawn. Nude mice were sacrificed the next day after drug withdrawal and the tumors were weighed. Treatment size of the xenografts were measured by vernier caliper. The tumor volume and tumor growth inhibiting rates were calculated and the curve tumor growth was drawn. The expression of NF-κBp65 was detected by immunohistochemistry in the xenografts. Results There were significant differences in average tumor vol- umes, inhibition rates and the photon number in the combined treatment group compared with the other groups （P 〈 0.05 ）. Compared with the control group and SN50 group, the average volumes and photon number of tumor were signif- icantly lower in 5-FU group, while the growth inhibition rates of tumor were significantly higher （P 〈 0.05 ）. No statisti- cal significances were found in average tumor volumes, inhibition rates and the photon number between SN50 group and control group （P 〉 0.05）. The positive rate of NF-κBp65 in each group as follows ： control group 47.4% , 5-FU group 57.1% , SN50 group 11.8% , 5-FU ＋ SN50 group 25.0%. Conclusion 5-FU only or combined with SN50 can inhibit gastric cancer tumor growth, and drug combination is more effective; SN50 can inhibit the activation of NF-κB signaling pathway to reduce expression of NF-κBp65 in tumor cells,

关 键 词：核转录因子-ΚB 胃癌 SN50 5-氟尿嘧啶 

分 类 号：R735.2[医药卫生—肿瘤]