Potassium channel blocker (4-AP) enhances the radiosensitivity of human cervical cancer cell line HeLa to <sup>252</sup>Cf neutron ray

林爽; 李力; 刘媛

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Potassium channel blocker (4-AP) enhances the radiosensitivity of human cervical cancer cell line HeLa to ²⁵²Cf neutron ray

更新时间：2026-01-09

- Potassium channel blocker (4-AP) enhances the radiosensitivity of human cervical cancer cell line HeLa to ²⁵²Cf neutron ray
- Journal of Army Medical University Vol. 30, Issue 10, Pages: 953-956(2008)
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  CLC： R730.55;R737.33;R965
- Published：2008
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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.
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. DOI：

　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. DOI：

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

252

Cf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（P0.05）。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（P0.01）。0.67 Gy

252

Cf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（P0.05）。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（P0.01）。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

252

Cf neutron ray. Methods HeLa cells were treated with 4-AP(0

20 mmol/L

respectively) and then exposed to 0.67 Gy

252

Cf 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

252

Cf neutron ray. Results After HeLa cells treated with 0

20 mmol/L 4-AP were exposed to 0.67 Gy

252

Cf 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 (P0.05). 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

252

Cf 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 P0.05). However

after treated with 20 mmol/L 4-AP and exposed to 0.67 Gy

252

Cf 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 (P0.01). Conclusion To HeLa cells exposed to

252

Cf neut

ron 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.

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Potassium channel blocker (4-AP) enhances the radiosensitivity of human cervical cancer cell line HeLa to 252Cf neutron ray

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摘要

Abstract

关键词

Keywords

references

Potassium channel blocker (4-AP) enhances the radiosensitivity of human cervical cancer cell line HeLa to ²⁵²Cf neutron ray