兰州大学机构库 >学院待认领
AG490调控人宫颈癌裸鼠移植瘤Survivin表达与STAT3信号通路的机制
Alternative TitleAG490 Regulates the Expression of Survivin and STAT3 signal transduction pathway of human cervical cancer xenografts in nude mice
马戎
Thesis Advisor王海琳
2009-05-12
Degree Grantor兰州大学
Place of Conferral兰州
Degree Name硕士
KeywordAG490 宫颈癌裸鼠移植瘤 Survivin P-STAT3
Abstract目的:探讨AG490对人宫颈癌裸鼠移植瘤生长、凋亡的影响以及调控Survivin 表达与Stat3信号转导通路的关系。 方法: 建立宫颈癌裸鼠移植瘤模型并分组,裸鼠背侧近右后肢处皮下接种人宫颈癌hela细胞,30 d 后分4 组治疗,每组8只动物。对照组,腹腔注射无菌生理盐水;DDP 组腹腔注射5mg/kg;AG490组腹腔注射8mg/kg ;DDP + AG490组腹腔注射DDP 5mg/kg+ AG490 8mg/kg;上述药物均每3 d 注射1 次,共注射4 次,于停药次日处死裸鼠。治疗期间观察并记录各组裸鼠皮下移植瘤的生长情况,计算肿瘤体积、肿瘤生长抑制率,绘制肿瘤生长曲线,观察用药后裸鼠体重变化。免疫组化、Western blot分别检测移植瘤P-STAT3、Survivin表达,流式细胞技术检测细胞凋亡。 结果:(1)各治疗组治疗后肿瘤体积和抑瘤率与对照组相比差异均具有统计学意义( P < 0. 05) ;与DDP 及AG490组比较,DDP + AG490联合用药组肿瘤体积明显减小( P < 0. 05),抑瘤率明显增高( P < 0. 05); AG490组与对照组比较体重变化无显著性差异(P=0.19)。(2)DDP组、AG490组和联合用药组凋亡率分别是52.1±1.3%、39.5±0.4%、66.7±1.8%,各组与对照组10.2±2.4%相比均有显著性差异(P<0.05)。(3)移植瘤HE染色肿瘤细胞平均坏死率为:对照组21.8±9.0%、AG490组39.4±11.3%、DDP组40.8±7.3%、DDP+AG490组61.9±9.6%,各组与对照组差异有统计学显著意义(P<0.05),DDP+AG490组与AG490组、DDP组差异有统计学意义(P<0.05)。(4)免疫组化结果 各组阳性率依次为:P-STAT3:对照组92.5%;DDP组64%;AG490组55%;DDP+AG490组40.9%;Survivin:对照组90.4%;DDP组53.9%;AG490组52.1%;DDP+AG490组36.8%;可见在对照组中P-STAT3、Survivin均为高表达,用药后表达有下降。 结论: 1.AG490与DDP单独及联合应用能抑制宫颈癌移植瘤生长,促进宫颈癌细胞凋亡,同时使宫颈癌细胞P-STAT3、Survivin表达与活性明显下降。2.联合应用AG490与DDP,可以起协同作用。3.AG490可以增强DDP的药物敏感性并且减轻药物副作用,JAK激酶抑制剂AG490与DDP联合应用可能为治疗宫颈癌提供了新的理论基础。
Other AbstractObjective: To investigate the effects of AG490 on human cervical cancer xenografts in nude mice growth and apoptosis,as well as the relationship between the expression of Survivin and STAT3 signal transduction pathway. Methods:Establish the model of human cervical cancer xenografts in nude mice, nude mice were subcutaneously implanted with human cervical cancer cancer Hale cell on the right side of nude mice’s back , and divided into 4 groups after 30 days :control group , DDP group ,AG490 group ,and AG490 with DDP group, AG490(8mg/kg) ,DDP(5mg/kg)and AG490 with DDP group(8mg/kg +5mg/kg )were administrated i.p. /3d , a total of 4 times injection in nude mice were killed the day after drug withdrawal.The tumor volumes and changes in body weight were measured respectively during the therapy time.The tumor growth inhibiting rates of each group were calculated,the curves of tumor growth were drew.The expression of p-STAT3 and Survivin by immunohistochemistry in the xenografts . Flow cytometry was applied to analyze the cell apoptosis. Results:(1)Significant differences in average tumor volumes and tumor growth inhibition rates were found between the treatment group and the control group( P < 0.05) . The tumor volumes in combination group were significantly less than those of other groups( P < 0. 05) . Compared with DDP group and AG490 group ,the growth inhibiting rates of tumor in combination group were significantly higher. AG490 group compared with the control group had no significant changes in body weight difference(P=0.19).(2) DDP group, AG490 group and the combined group apoptosis rate of 52.1%, 39.5%, 66.7%, the control group do not form a clear-apoptosis, Each group with the control group compared to 10.2 ± 2.4% were significantly different(P<0.05).(3) tumor necrosis rate of the average: the control group 21.8 ± 9.0%, AG490 group 39.4 ± 11.3%, DDP group 40.8 ± 7.3%, DDP + AG490 group 61.9 ± 9.6%, Each group with the control group compared were significantly different(P<0.05), Significant differences in DDP + AG490 group Compared with DDP group and AG490 group(P<0.05).(4)SP The positive rate of each group were: P-STAT3: the control group 92.5%; DDP group 64%; AG490 group 55%; DDP +AG490 group 40.9%; Survivin: control group, 90.4%; DDP group 53.9%; AG490 group 52.1%; DDP +AG490 group 36.8 percent; in the control group have a high expression about P-STAT3 and Survivin, diminishing the expression of P-STAT3,Survivin after the therap...
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Language中文
Document Type学位论文
Identifierhttps://ir.lzu.edu.cn/handle/262010/224241
Collection学院待认领
Affiliation临床医学院
Recommended Citation
GB/T 7714
马戎. AG490调控人宫颈癌裸鼠移植瘤Survivin表达与STAT3信号通路的机制[D]. 兰州. 兰州大学,2009.
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