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目的探讨吩噻嗪衍生物对人宫颈癌HeLa细胞增殖的抑制作用及与放射联合应用抑制肿瘤的协同效应。方法采用MTT法和细胞克隆形成法检测细胞的增殖活性和细胞辐射敏感性。结果比较了6种吩噻嗪衍生物对HeLa细胞增殖的抑制效应,发现化合物α氯N二甲胺基乙基吩噻嗪(PTZD2)、α三氟甲基N二甲胺基乙基吩噻嗪(PTZD3)和α氯N二乙胺基乙基吩噻嗪(PTZD5)的作用比较明显,在10μmol L浓度能产生出显著抑制效应,40～50μmol L浓度作用3和4d,细胞增殖完全被抑制而死亡。PTZD2或PTZD3与放射联合应用,显示出明显抗HeLa细胞增殖的协同效应,10μmol LPTZD3对2和4Gy照射细胞的增殖抑制的增强比分别为3.5和1.8。实验结果还表明,在照射前18h用药的协同作用更加显著。结论吩噻嗪衍生物具有程度不同的抑制HeLa细胞增殖的作用,与放射联合应用具有抗肿瘤的协同效应,而且照射前18h用药的效应最佳。
Objective To investigate the inhibitory effect of phenothiazine derivatives on the proliferation of human cervical cancer HeLa cells and the synergistic effect of radiotherapy combined with radiation on tumor suppression. Methods MTT assay and cell clone formation assay were used to detect cell proliferation activity and cell radiation sensitivity. Results The inhibitory effects of 6 phenothiazine derivatives on HeLa cell proliferation were compared. It was found that the compounds α-chloro-N-dimethylaminoethylphenothiazine (PTZD2), α-trifluoromethyl N-dimethylaminoethylphenothiazine The effects of PTZD3 and PTZD5 were obvious. The inhibitory effect was obvious at the concentrations of 10μmol L and 40 and 50μmol L for 3 and 4 days respectively. Cell proliferation was completely inhibited Inhibition and death. The combination of PTZD2 or PTZD3 with radiation showed a synergistic effect on the proliferation of HeLa cells. The enhancement ratio of 10 μmol LPTZD3 on the proliferation inhibition of 2 and 4 Gy irradiated cells was 3.5 and 1.8, respectively. The experimental results also show that the synergistic effect of the drug 18h before irradiation is more significant. Conclusion Phenothiazine derivatives have different degrees of inhibition of HeLa cell proliferation, combined with radiation has anti-tumor synergistic effect, and 18h before irradiation the best effect.