[1]林爽,李力,刘媛.钾通道阻断剂四氨基吡啶增加宫颈癌细胞对中子照射的敏感性[J].陆军军医大学学报(原第三军医大学学报),2008,30(10):953-956.
 LIN Shuang,LI Li,LIU Yuan.Potassium channel blocker (4-AP) enhances the radiosensitivity of human cervical cancer cell line HeLa to 252Cf neutron ray[J].J Amry Med Univ (J Third Mil Med Univ),2008,30(10):953-956.
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钾通道阻断剂四氨基吡啶增加宫颈癌细胞对中子照射的敏感性(/HTML )
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陆军军医大学学报(原第三军医大学学报)[ISSN:1000-5404/CN:51-1095/R]

卷:
30卷
期数:
2008年第10期
页码:
953-956
栏目:
论著
出版日期:
2008-05-30

文章信息/Info

Title:
Potassium channel blocker (4-AP) enhances the radiosensitivity of human cervical cancer cell line HeLa to 252Cf neutron ray
作者:
林爽李力刘媛
第三军医大学大坪医院野战外科研究所:妇产科, 第三研究室,创伤、烧伤与复合伤国家重点实验室
Author(s):
LIN Shuang LI Li LIU Yuan
Department of Obstetrics and Gynecology, State Key Laboratory of Trauma, Burns and Combined Injury, Department 3, Institute of Surgery Research, Daping Hospital, Third Military Medical University
关键词:
钾通道阻滞剂四氨基吡啶宫颈癌252Cf中子照射
Keywords:
potassium channel blocker 4-amino-pynidine cervical cancer 252Cf neutron
分类号:
R730.55;R737.33;R965
文献标志码:
A
摘要:
目的  研究钾通道阻断剂四氨基吡啶(4-amino-pynidine, 4-AP)对宫颈癌HeLa细胞中子照射的影响。  方法  宫颈癌HeLa细胞分别设不同浓度(0、1、5、10、20 mmol/L)4-AP组,0.67 Gy 252Cf中子照射后48 h,用MTT法和流式细胞仪检测各组细胞活性、凋亡率。0、20 mmol/L 4-AP组自照射后24、48、72 h分别用RT-PCR法、Western blot法检测HIF-1α  mRNA 及蛋白表达情况。  结果  在中子照射48 h后,4-AP浓度为0、1、5、10、20 mmol/L时,对HeLa细胞增殖的抑制率分别为0、(38.81±3.45)%、(46.63±3.88)%、(63.58±6.19)%、(77.51±8.87)%,凋亡率(%)分别为(3.15±0.85)%、(8.01±1.19)%、(16.00±1.58)%、(47.20±3.18)%、(62.56±4.27)%,差异有统计学意义(P<0.05)。说明4-AP能抑制HeLa细胞的增殖,诱导凋亡,并呈现明显的剂量依赖性。当4-AP浓度大于5 mmol/L时,其作用明显(P<0.01)。0.67 Gy 252Cf中子照射0、24、48、72 h后,4-AP浓度为0 mmol/L 组,HIF-1α mRNA/β-actin值分别为(0.423±0.116)、(0.464±0.111)、(0.487±0.121)、(0.415±0.099),Western blot灰度扫描结果HIF-1α/β-actin分别为(0.723±0.116)、(0.664±0.111)、(0.617±0.121)、(0.515±0.099),HIF-1α mRNA及蛋白表达均无明显降低,差异均无统计学意义(P>0.05)。4-AP浓度为20 mmol/L 组, HIF-1α mRNA/β-actin值分别为(0.401±0.121)、(0.364±0.142)、(0.257±0.137)、(0.165±0.099),Western blot灰度扫描结果HIF-1α mRNA/β-actin分别为(0.879±0.117)、(0.645±0.115)、(0.312±0.114)、(0.130±0.118),HIF-1α mRNA及蛋白表达均明显降低,差异有统计学意义(P<0.01)。  结论  钾通道阻断剂4-AP能降低中子放射治疗后缺氧诱导因子(HIF-1α)表达,降低HeLa细胞增殖,促进凋亡,提高HeLa细胞中子射线的敏感性。
Abstract:
Objective  To investigate the potential effect of 4-amino-pynidine (4-AP) on human cervical carcinoma cell line HeLa to 252Cf neutron ray.   Methods  HeLa cells were treated with 4-AP(0, 1, 5, 10, 20 mmol/L, respectively) and then exposed to 0.67 Gy 252Cf neutron ray. The effect of 4-AP on proliferation of HeLa cells was assessed by MTT assay. Cell apoptosis were detected by flow cytometry. Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to investigate the levels of HIF-1α mRNA and protein of HeLa cells treated with 4-AP (0, 20 mmol/L) and 0.67 Gy 252Cf neutron ray.   Results  After HeLa cells treated with 0, 1, 5, 10, 20 mmol/L 4-AP were exposed to 0.67 Gy 252Cf neutron ray for 48 h, their inhibitory rate was 0, (38.81 ±3.45)%, (46.63±3.88)%, (63.58±6.19)%, (77.51±8.87)%, and their apoptotic rate was (3.15±0.85)%, (8.01±1.19)%, (16.00±1.58)%, (47.20±3.18)%, (62.56±4.27)%, respectively, suggesting 4-AP may inhibit the proliferation of HeLa cells and induce their apoptosis in a dose-dependent manner (P<0.05). Of HeLa cells treated with 0 mmol/L 4-AP, the optical density ratio of HIF-1α mRNA/β-actin was (0.423±0.116), (0.464±0.111), (0.487±0.121), (0.415±0.099) after 24-, 48- and 72-hour exposure to 0.67 Gy 252Cf neutron ray, while the optical density ratio of HIF-1α protein/β-actin was (0.723±0.116), (0.664±0.111), (0.617±0.121), (0.515±0.099) (both P>0.05). However, after treated with 20 mmol/L 4-AP and exposed to 0.67 Gy 252Cf neutron ray for 24, 48 and 72 h, the optical density ratio of HIF-1α mRNA/β-actin of HeLa cells was (0.401±0.121), (0.364±0.142), (0.257±0.137), (0.165±0.099), while the optical density ratio of HIF-1α protain/β-actin were (0.879±0.117), (0.645±0.115), (0.312±0.114), (0.130±0.118), showing that the levels of HIF-1α mRNA and protein both declined (P<0.01).   Conclusion  To HeLa cells exposed to 252Cf neutron ray, potassium channel blocker (4-AP) pretreatment inhibits their HIF-1α expression and their proliferation and promote their apoptosis. The potassium channel blocker (4-AP) significantly enhances the sensitivity of HeLa cells to neutron radiotherapy.
更新日期/Last Update: 2008-05-27