4-羟苯基维胺脂对宫颈癌HeLa细胞系的放射增敏作用

Radiosensitization effect of N-4-hydroxyphenyl retinode on cervical carcinoma cell line HeLa

目的探讨4-羟苯基维胺脂(4-HPR)对HeLa细胞生长抑制和凋亡的影响;研究小剂量4-HPR对HeLa细胞的放射增敏效应。方法用四甲基偶氮唑蓝比色法(MTT)观察4-HPR对HeLa细胞的生长抑制情况;电镜观察4-HPR、放疗处理后HeLa细胞超微结构的改变;流式细胞仪检测单用4-HPR、γ-射线以及2者联合使用时HeLa细胞凋亡率和细胞周期变化。结果4-HPR和2 Gy60Co照射单独作用均可引起HeLa细胞超微结构改变,发生早期凋亡,4-HPR低剂量组(1μmol.L-1,2μmol.L-1)、单纯放射组与无药对照组凋亡率比较无统计学差异(P>0.05);4-HPR 4μmol.L-1组与无药对照组有显著性差异(P<0.01)。2 Gy60Co照射和4-HPR(2μmol.L-1,4μmol.L-1)联合使用细胞凋亡率较单纯放射组凋亡率有显著性差异(P<0.05,P<0.01);4-HPR作用后,HeLa细胞周期发生变化,表现为G1期减少,S期增加。结论4-HPR可诱导肿瘤细胞凋亡,小剂量4-HPR可增加HeLa细胞对放疗的敏感性。

Objective To investigate the growth suppression and apoptosis inducing effect of N-4-hydroxyphenyl retinode （4-HPR） on human HeLa cell lines,and to study the role of low dose 4-HPR in the increase of HeLa cell line＇s radiotherapy sensitivity. Methods MTT assay was employed to examine the growth suppression of the cells. TEM was used to observe the ultrastructural change of HeLa cells treated with 4-HPR and γ-ray. The apoptosis rate and change in cell cycle of HeLa cells treated with 4-HPR or/and γ-ray were examined by flow cytometer. Results 4-HPR and radiation（2 Gy ^60Co） both could induce pristine apoptosis of HeLa cells ; while there were no significant difference between apoptosis rate of 4-HPR （ 1 μmol·L^-1, 2 μmol·L^-1） ,simple radiation（2 Gy ^60Co） and apoptosis rate of control group （P 〉0.05） ,there was significant difference between apoptosis rate of 4-HPR 4μmol·L^-1 and apoptosis rate of control group （ P 〈 0. 01 ）. Combined use of 4-HPR （2 μmol·L^-1 ,4 μmol·L^-1 ） and radiation（2 Gy ^60Co） ,the apoptosis rate were significant different from the apoptosis rate of simple radiation group（P 〈0.05 ,P 〈0.01 ） ;and 4-HPR could change cell cycle of HeLa cell lines with G, phase cells decreasing and S phase cells increasing. Conclusion 4-HPR can induce apoptosis of HeLa cells,and low dose 4-HPR can enhance the sensitivity of radiotherapy.