脱氧氟尿苷增强顺铂对人肝癌BEL-7402细胞株的增殖抑制作用  

Synergistically suppressive effect of 5-DFUR and cisplatin on the proliferation of human hepatoma cell line BEL-7402

作　　者：唐浩[1] 梁平[2] 李荣萍[3] 周亚龙[1] 

机构地区：[1]解放军第187中心医院肝胆外科,海口571159 [2]第三军医大学新桥医院普外科 [3]第三军医大学新桥医院消化科

出　　处：《中华普通外科杂志》2007年第9期669-671,共3页Chinese Journal of General Surgery

摘　　要：目的 探讨脱氧氟尿苷（5-DFUR）和顺铂（CDDP）联合应用对人肝癌细胞系BEL-7402的增殖抑制作用。方法 采用克隆形成法检测细胞的增殖抑制率、流式细胞术检测细胞周期的改变及凋亡率。结果 5-DFUR（7.815～250mg/L）和CDDP（0.63～20mg/L）单独应用均对人肝癌BEL- 7402细胞有抑制作用，呈现剂量效应关系。5-DFUR与CDDP联合应用对人肝癌细胞BEL-7402产生显著的协同杀伤作用，5-DFUR与CDDP浓度接近IC50时即5-DFUR 62.5mg/L与CDDP 2.5mg/L联合用药时可使CDDP的抑制率从单独用药的45.12%提高到联合用药的89%（P〈0.01）。CDDP、5-DFUR单独应用48h后可诱导人肝癌BEL-7402细胞发生凋亡，凋亡比率分别为15.37%和21.25%，联合用药组在48h细胞凋亡的比率则为19.37%，72h后CDDP、5-DFUR单独应用诱导人肝癌BEL-7402细胞发生凋亡的比率分别为19.3%和28.37%，而联合应用组诱导凋亡细胞的比例达到55.7%（P〈0.01），CDDP与5-DFUR单用72h时，细胞周期G1期阻滞较为明显，而当5-DFUR与CDDP合用后，G1期、S、G2期/M期细胞增加，尤其是G2期/M期细胞数增加明显。结论 5-DFUR与CDDP联合应用对人肝癌细胞BEL-7402可产生显著的协同杀伤作用，其细胞周期调节发生在G2～M期，细胞被阻滞于G2～M期。Objective To investigate the proliferation-suppressing effect of doxifluridine （5-DFUR） and cisplatin （CDDP）used in combination on human liver cancer BEL-7402 cells. Methods Cell proliferation-suppressing rates were determined by colony-forming assay, and apoptotic changes and apoptotic rates were assessed by flow cytometry. Results Doxifluridine （7. 815 -250 mg/L） and cisplatin （0.63 -20 mg/L） used alone inhibited the proliferation of human liver cancer BEL-7402 cells in a dose-dependent manner. 5-DFUR and CDDP used in combination significantly increased the killing effect on human liver cancer BEL-7402 cells in a synergistic manner. In particular, with the concentrations of 5-DFUR and CDDP approaching their respective IC50 values （ i. e, 62.5 mg/L for 5-DFUR and 2. 5 mg/L for CDDP）, the combined use of both drugs increased the cell proliferation-suppressing rate of CDDP from 45. 12% to approximately 89% （ P 〈0. 01 ）. In addition, after CDDP and 5-DFUR having been used alone for 48 h, apoptosis of BEL-7402 cells can be induced, with the apoptotic rates of 15. 37 % and 21.25 %, respectively. In the combined medication group, the apoptotic rate of cells after 48 h of induction was 19. 37%, being not significantly different from that in the single-drug groups. Nevertheless, after 72 h of induction, CDDP and 5-DFUR used alone gave rise to apoptotic rates of 19. 3 % and 28. 37%, respectively, while CDDP and 5-DFUR used in combination resulted in an apoptotic rate of 55.7% （ P 〈 0. 01 ）. After 72 h of induction, when CDDP and 5-DFUR were used alone, apoptotic cells showed obvious G1 phase arrest. However, when 5-DFUR and CDDP were used in combination, apoptotic cells mainly displayed increases in cells at G1, S, G2/M phases, particularly in cells at G2/M phase. Conclusions When used in combination, 5-DFUR and CDDP significantly killed human liver cancer BEL-7402 cells in a synergistic manner, and their regulation on apoptosis occurred at G2-M phases, and cells were arrested at G2-M phas

关 键 词：癌 肝细胞 细胞周期 细胞凋亡 脱氧氟尿苷 顺铂 

分 类 号：R686[医药卫生—骨科学]