组蛋白去乙酰酶抑制剂联合抗癌药物抑制膀胱癌的实验研究

Inhibitory effect of histone deacetylase inhibitor MS-275 combined with chemotherapy on bladder cancer cell: An experimental study

目的观察组蛋白去乙酰酶抑制剂MS-275联合针对DNA的化疗药物对膀胱癌T24细胞的抑制作用。方法用MTT法测定MS-275单用及分别与阿霉素、丝裂霉素C和顺铂联用对T24细胞的抑制率,用金氏公式法判断联合用药的效果。结果MS-275分别与阿霉素、丝裂霉素C、顺铂联合用药对T24细胞的抑制率均随着浓度的增加而明显增加,MS-275与丝裂霉素C联用的协同作用最明显,而MS-275与阿霉素和顺铂在中低剂量下联用亦表现为协同作用。结论组蛋白去乙酰酶抑制剂可明显增强针对DNA的化疗药物对膀胱癌细胞的细胞毒作用,因此可为应用于晚期膀胱癌的化疗方案提供可能。

Objective To investigate the cytotoxic activity of histone deacetylase（HDAC） inhibitor MS- 275 combined with anticancer drugs targeting DNA on T24 bladder cancer cell line. Methods MTr assay was used to detect the inhibitory rate of MS-275 alone or combined with adriamycin （ADM）, mitomycin C （MMC） and cisplatin （DDP） respectively on T24 bladder cancer cell. Jin＇s equation was used to evaluate the effectiveness of drug combination. Results The cell inhibition rates MS-275 combined with ADM, MMC and DDP respectively were in a concentration-dependent manner. The synergism of MS-275 combined with MMC was most significant. When administered in lower or moderate concentration, MS-275 combined with ADM or DDP demonstrated synergic effect too. Conclusion HDAC inhibitor can enhance the cytotoxic activity of anticancer drugs targeting DNA on bladder cancer ceils and is promising to be used in chemotherapeutic regimens for advanced bladder cancer.