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黄芪超滤物对H22腹水瘤小鼠重离子放疗的增敏作用及机制探讨     被引量:6

Enhanced radiosensitivity of H22 ascitic tumor to ^(12)C^(6+) ions radiation in ultra-filtration extract mixture from Astragalus mongholicus-treated mice

文献类型:期刊文献

中文题名:黄芪超滤物对H22腹水瘤小鼠重离子放疗的增敏作用及机制探讨

英文题名:Enhanced radiosensitivity of H22 ascitic tumor to ^(12)C^(6+) ions radiation in ultra-filtration extract mixture from Astragalus mongholicus-treated mice

作者:汪彬彬[1,2];王小虎[1,2];刘凯[1,3];孙少伯[1,3];宋鹏[1,3];李应东[1,3]

第一作者:汪彬彬

机构:[1]甘肃中医药大学中西医结合学院,甘肃兰州730000;[2]甘肃省肿瘤医院,甘肃兰州730050;[3]甘肃省中医药防治慢性疾病重点实验室甘肃兰州730000

第一机构:甘肃中医药大学中西医结合学院

年份:2015

卷号:50

期号:12

起止页码:1596

中文期刊名:药学学报

外文期刊名:Acta Pharmaceutica Sinica

收录:CSTPCD;;Scopus;北大核心:【北大核心2014】;CSCD:【CSCD2015_2016】;PubMed;

基金:国家自然科学基金资助项目(81160478);甘肃省重离子等射线治疗肿瘤研究科技创新团队资金(098TTCA009);甘肃省2009年科技重大专项(092NKDA017)

语种:中文

中文关键词:黄芪超滤物;12C6+离子束外照射;放射增敏;p53

外文关键词:ultra-filtration extract mixture from Astragalus mongholicus; 12C6+ ion beam radiotherapy;radiosensitization; p53

摘要:观察黄芪超滤物(UEMAM)对H22腹水瘤小鼠重离子放疗的增敏作用,并探讨其相关的机制。小鼠腹腔内注射H22腹水瘤细胞悬液0.2 mL制备腹水瘤小鼠模型。成模小鼠随机分为4组,分别给予生理盐水(对照组)、UEMAM(中药组)、6Gy^(12)C^(6+)离子束外照射(放疗组)及UEMAM联合6Gy^(12)C^(6+)离子束外照射(中药+放疗组)处理。每天测量小鼠的体重、腹围,并观察其日常生活状态;统计各组小鼠的生存期,流式细胞仪检测细胞的凋亡率及周期分布;Western blot检测p53、Bax、Bcl-2及cleaved Caspase-3的表达;单细胞凝胶电泳技术观察H22细胞DNA的损伤情况。实验结果表明治疗组(中药组、放疗组及中药加放疗组)小鼠平均生存时间较对照组明显延长,体重与腹围较对照组明显减小;与对照组相比,治疗干预后促进了H22细胞凋亡、周期阻滞及DNA损伤;中药加放疗组的平均生存时间较放疗组明显延长,体重与腹围较放疗组明显减小;此外,中药加放疗组还促进了H22细胞凋亡、周期阻滞及DNA损伤;蛋白表达结果分析治疗组(中药组、放疗组及中药加放疗组)明显激活了p53凋亡信号通路。通过该实验发现UEMAM对H22腹水瘤小鼠具有放射增敏作用,其增敏作用机制与激活p53介导的细胞凋亡信号途径有关。
This study was designed to investigate the impact of ultra-filtration extract mixture from Astragalus mongholicus (UEMAM) on radiosensitivity of H22 ascitic tumor in mice to 12C6+ ions radiation. The H22 ascitic tumor model was established in mice by intraperitoneal injection of 0.2 mL H22 ascitic cells. The animals were subsequently divided into 4 groups randomly, treated with normal saline, UEMAM, heavy ion beam radiotherapy and UEMAM plus heavy ion beam radiotherapy, respectively. The body weights, abdomen circumference of the mice were measured and the mouse behavior was monitored every day; survival time was recorded to evaluate life extension effect; flow cytometry technique was used to detect H22 cell apoptosis and cell cycle; protein levels of p53, Bax, Bcl-2 and cleaved Caspase-3 were analyzed by Western blot; the single cell gel electrophoresis was used to detect the level of deoxyribonucleic acla oamage tLP^s,~ uam^t~). results suggest that UEMAM significantly increased survival time, and decreased body weights and abdomen circumference over the saline control group. The treatment increased cell apoptosis, cycle arrest and DNA damage compared to the saline control group. UEMAM significantly enhanced the therapeutic effect of heavy ion beam radiation in survival time, and decreased body weights and abdomen circumference in the tumor-baring mice. The combination increased cell apoptosis, cycle arrest and DNA damage compared to the radiotherapy group. The results of Western blot suggest that the treatment significantly enhanced p53-induced apoptotic signals. The experiment discovered that UEMAM could improve radiosensitivity of H22 ascitic tumor through activation ofp53-rnediated apoptotic signal pathway.

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