摘要
探究二甲双胍联合单次高剂量放疗对小鼠非小细胞肺癌的治疗机制和效果。体外细胞试验:通过细胞存活曲线评价二甲双胍在不同氧和葡萄糖含量条件下的细胞毒性。体内异种移植瘤试验:将NSCLC-A549细胞注入小鼠,分为对照组、单独给予二甲双胍组、单独接受单次高剂量放疗组、放疗前1 h给予二甲双胍组和放疗后24 h给予二甲双胍组。评价各组肿瘤生长情况,对肿瘤组织进行血流量和组织学分析。体外试验结果显示:低氧低糖条件下二甲双胍细胞毒性最高。肿瘤生长结果显示:单次高剂量放疗前1 h和后24 h给予二甲双胍组小鼠肿瘤体积最小((0.47±0.12)cm^(3)vs(0.49±0.21)cm^(3))。血流量分析结果显示:单次高剂量放疗破坏了肿瘤组织微血管,降低了氧和葡萄糖灌注。组织学分析结果显示:肿瘤组织中心低氧低糖区域细胞优先被二甲双胍杀死,周围灌注较好区域存在存活细胞。二甲双胍联合单次高剂量放疗可通过改变肿瘤细胞代谢增强毒性,试验结果为未来二甲双胍联合立体定向放疗提供了理论和数据支持。
To explore the therapeutic effect of metformin combined with single high-dose radiotherapy in mice with non-small cell lung cancer and the mechanism involved. In vitro cell test: the cytotoxicity of metformin under different oxygen and glucose contents was evaluated using cell survival curves. In vivo xenograft tumor test:NSCLC-A549 cells were injected into mice, which were then divided into the following five groups: control group,metformin group, single high-dose radiotherapy group, metformin 1 h before radiotherapy group, and metformin24 h after radiotherapy group. Growth of the tumor was evaluated in each group, and the blood flow and histology of the tumor tissues were analyzed. According to the in vitro test results, metformin was the most cytotoxic under hypoxic and low-glucose conditions. The in vivo results showed that the tumor volume was the smallest in the mouse groups administered metformin 1 h before high-dose radiotherapy and 24 h after radiotherapy((0.47±0.12) cm^(3)and(0.49±0.21) cm^(3), respectively). Blood flow analysis showed that single high-dose radiotherapy destroyed the microvessels of tumor tissue and reduced the perfusion of oxygen and glucose. Histological analysis revealed that cells in hypoxic and hypoglycemic area of the tumor tissue center were preferentially killed by metformin, whereas there were viable cells in the surrounding well perfused areas. Metformin combined with single high-dose radiotherapy enhanced the toxicity by changing tumor cell metabolism. These results provide theoretical and data support for the future use of metformin combined with stereotactic body radiotherapy.
作者
李慧超
赵明娟
田龙
LI Huichao;ZHAO Mingjuan;TIAN Long(The First Affiliated Hospital of Hebei Northern University,Zhangjiakou 075000,China;Hebei General Hospital,Shijiazhuang 050000,China)
出处
《辐射研究与辐射工艺学报》
CAS
CSCD
2022年第6期23-28,共6页
Journal of Radiation Research and Radiation Processing
基金
张家口市重点研发计划项目(1921002B)资助。
关键词
非小细胞肺癌
二甲双胍
单次高剂量放疗
作用机制
Non-small cell lung cancer
Metformin
Single high-dose radiotherapy
Action mechanism
