6-溴异香兰素对HeLa细胞的增殖抑制及放射增敏作用

目的研究香兰素衍生物中的6-溴异香兰素（6-溴-5-羟基-4-甲氧基苯甲醛,BVAN08）对HeLa细胞增殖和放射敏感性的影响,为开发新的抗癌和放射增敏药物提供理论依据。方法利用MTT法检测细胞增殖,单细胞凝胶电泳检测细胞DNA损伤,流式细胞术检测细胞周期,克隆形成率法检测细胞放射敏感性,AnnexinⅤ/PI染色法检测细胞凋亡。结果研究表明BVAN08在10～20μmol/L以上浓度就显示出对HeLa细胞增殖的抑制作用,抑制程度具有剂量依赖性,抑制细胞存活的IC50值为19.07μmol/L。BVAN08能诱发细胞DNA双链断裂损伤,作用4h就开始诱发细胞周期G2/M阻滞,随时间延长阻滞更加明显。BVAN08明显降低DNA修复蛋白DNA-PKcs的表达水平,20μmol/LBVAN08与2Gyγ射线复合作用可以显著增加细胞对射线的敏感性,增加细胞凋亡率。结论 BVAN08抑制HeLa细胞增殖,提高细胞的放射敏感性,其放射增敏作用与降低DNA-PKcs蛋白表达水平和G2/M阻滞有关。

Proliferation inhibition and radiosensitization effects of 6-bromoisovanillin on HeLa cells

Objective To study the effects of 6-bromoisovanillin（6-bromine-5-hydroxy-4-methoxy-benzaldehyde,BVAN08）on the proliferation and radiosensitivity of cultured HeLa cells,and to provide experimental data and advanced evidence for exploring anticancer and radiation-sensitizing new drugs.Methods MTT assay was used to detect cell proliferation,the DNA damage was detected by single-cell gel electrophoresis.Flow cytometry was used to monitor cell cycle changes,colony-forming ability assay was used to analyze the radiosensitivity,and apoptosis was detected by AnnexinⅤ/PI staining.Results BVAN08 suppressed the proliferation of HeLa cells at the concentrations over 10-20 μmol/L in a dose-dependent manner.The survival cure analysis indicated that the IC50 was 19.07 μmol/L.DNA double-strand breaks were also detected in the cells after the treatment with BVAN08.BVAN08 initiated a G2/M phases arrest four hours after treatment.The accumulation of G2/M population increased with the duration of treatment.The expression of DNA repair protein DNA-PKcs was remarkably depressed by BVAN08.Combined treatment with 20 μmol/L BVAN08 and 2 Gy ~（60）Co γ-rays significantly decreased the cell survival and increased the induction of apoptosis.Conclusion BVAN08 can inhibit proliferation and enhance the radiosensitivity of HeLa cells.The radiosensitization is related to the suppression of DNA-PKcs and G2/M phase arrest.[