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/L PTZD3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 examine the antiproliferative effects of phenothialzine derivatives (PTZDs) alone on HeLa cells and in combination with ionizing radiation. Methods MTT and colony-forming method were used to evaluate the proliferation activity and cellular radiosensitivity of HeLa cells. Results We compared the antiproliferative effects of six phenothialzine derivatives, and found that the derivatives α-chloro-N- dimethylamine phenothialzine (PTZD2), α-triflumethyl-N- α dimethylamine ethyl) phenothialzine ( PTZD3 ) and α-chloro-N-( dimethylamine ethyl) phenothialzine (PTZD5) showed a significant antiproliferative effect at concentration of 10 μmol/L. HeLa cells proliferation was completely suppressed when treated with PTZDs of 40-50 μmol/L. PTZD2/PTZD3 and colbat-60 gamma-irradiation showed synergistic suppressive effect on proliferation of HeLa cells. The enhancement ratios of 10 μmol/L PTZD3 combination with 2 Gy and 4 Gy irradiations were 3.5 and 1.8, respectively. The maximum synergistic suppressive effect was observed when cells administered with PTZD3 at 18 h before being irradiated. Conclusion Phenothialzine derivatives show antiproliferations on HeLa cells, and differ in degrees. The synergistic anticancer effect could be obtained by combining phenothialzine derivatives with radiotherapy.