机构地区:[1]上海中医药大学附属龙华医院肿瘤一科,上海200032
出 处:《中国临床药理学与治疗学》2014年第5期481-487,共7页Chinese Journal of Clinical Pharmacology and Therapeutics
基 金:国家自然科学基金项目(81373861);上海市卫生系统优秀学科带头人培养计划(XBR2013103);国家中医临床研究基地"龙医团队;龙医学者"项目(LYTD-05)
摘 要:目的:研究PTBP3对胃癌细胞中Bcl-2、Stat3基因表达的影响并探讨健脾类复方胃肠安(WCA)治疗胃癌与调控胃癌细胞中PTBP3等多基因表达相关的机制。方法:用稳定转染沉默PTBP3基因的人胃癌细胞株MKN45建立相应的裸小鼠皮下移植瘤模型,随机分为WCA高、低剂量组、5-FU组和生理盐水对照组,观察PTBP3基因以及WCA对移植瘤生长的影响。Real-time Quantitative PCR和Western Blot检测移植瘤细胞内PTBP3、Bcl-2和Stat3基因的mRNA和蛋白表达。结果:在PTBP3沉默模型和未沉默模型中,WCA高、低剂量组和5-FU组瘤重均低于同模型生理盐水组,差异均有统计学意义(P均为0.000);PTBP3沉默模型瘤重低于未沉默模型,差异有统计学意义(P=0.000)。Real-time Quantitative PCR和Western Blot检测示:与未沉默模型比较,PTBP3沉默模型中,PTBP3、Bcl-2和Stat3基因的mRNA表达下调,差异有统计学意义,PTBP3、Bcl-2和Stat3蛋白表达水平同样下调;PTBP3未沉默模型中,与生理盐水组比较,WCA高、低剂量组和5-FU组PTBP3、Bcl-2和Stat3基因的mRNA表达水平下调,差异有统计学意义,PTBP3、Bcl-2、Stat3基因的蛋白表达水平均低于生理盐水组;在PTBP3沉默模型中,WCA高、低剂量组和5-FU组PTBP3基因的mRNA和蛋白表达与生理盐水组比,差异无统计学意义,WCA组Bcl-2、Stat3的mRNA表达均低于生理盐水组,差异有统计学意义,其蛋白表达水平也下调。结论:PTBP3可上调胃癌细胞中Bcl-2、Stat3基因的表达;WCA抑瘤机制与其下调MKN45细胞中PTBP3、Bcl-2、Stat3等多基因的表达有关。AIM: To study the effect of PTBP3 on the expression of Bcl-2, Stat3 in human gastric cancer ceils, researching the related mechanisms between the anti-tumor effect of Wei Chang An (WCA) with regulated the expression of PTBP3 and other genes in gastric cancer cells. METHODS: Balb/c mice were planted MKN-45 cancer cells which were stably transfected with the Plasmids contained the siRNA Of PTBP3 to establish experimental model, after that were randomizedly divided into WCAhigh dose group, WCA low dose group, 5-FU group and control group. The effects of PTBP3 and WCA on the tumor growth were observed. The mRNA and protein expression of PTBP3, Bcl-2 and Stat3 were detected with Utilized Realtime Quantitative PCR and Western Blot. RESULTS:In the silencing PTBP3 model and no-silencing PTBP3 model, the tumor weights of WCA high and low dose group and 5-FU group were lower than those in the control group in the same model, the differences were statisticallysignificant (P values all are 0. 000); the tumor weight of silencing PTBP3 model was lower than that in the no-silencing PTBP3 model, the difference was statistically significant (P = 0. 000). Real-time Quantitative PCR and Western Blot showed, compared with the no-silencing PTBP3 model, in the silencing PTBP3 model, the mRNA expression of PTBP3, Bcl-2 and Stat3 were down regulated, the difference was statistically significant, the protein expression of PTBP3, Bcl-2 and Stat3 were down regulated too. In the no-silencing PTBP3 model, compared with the control group, the mRNA expression of PTBP3, Bcl-2 and Stat3 in WCA groups and 5- FU group were down regulated, the difference was statistically significant, the protein expression of PTBP3, Bcl-2 and Stat3 were down regulated too. In the silencing PTBP3 model, there was no significant difference between WCA groups, 5-FU group with control group on the mRNA and protein expression of PTBP3; the mRNA expression of Bcl-2 and Stat3 in WCA groups were lower than those in the control group, the difference was s
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