二氯乙酸钠联合顺铂对胃癌细胞的抑制作用  

Inhibitory effects of sodium dichloroacetate combined with cisplatin on gastric cancer cells

作　　者：刘小军[1] 刘敏[2] 段玲[1] 张涛[1] 乔慧[1] 赵达[1] 

机构地区：[1]兰州大学第一医院肿瘤内科,甘肃兰州730000 [2]兰州大学第一医院消化科,甘肃兰州730000

出　　处：《中国肿瘤生物治疗杂志》2016年第1期30-35,共6页Chinese Journal of Cancer Biotherapy

基　　金：甘肃省自然科学基金资助项目(No.145RJZA036);兰州大学第一医院院内基金资助项目(No.ldyyynjx201112)~~

摘　　要：目的:研究丙酮酸脱氢酶激酶抑制剂二氯乙酸钠(sodium dichloroacetate,DCA)对胃癌细胞的体外抗肿瘤效应。方法:使用不同浓度的DCA分别干预处理体外培养的胃癌SGC-7901和BGC-823细胞24 h,MTT法检测胃癌细胞存活率,中位效应法观察DCA联合顺铂(cisplatin,DDP)干预的协同效应,Transwell小室实验检测胃癌细胞的侵袭性,流式细胞术双染法检测细胞的早期凋亡率。结果:DCA(20、40、60、80和100 mmol/L)以浓度依赖方式显著抑制胃癌SGC-7901和BGC-823细胞增殖,24 h的IC_(50)值分别为60.9 mmol/L和53.8 mmol/L;较小剂量(20、40 mmol/L)DCA和DDP(5、10μmol/L)联合干预SGC-7901和BGC-823细胞的联合指数值均<1,提示两者具有协同抑制胃癌细胞增殖的效应。与对照组相比,DCA(60、80、100 mmol/L)组SGC-7901细胞穿膜数目显著降低[(99.3±11.7)、(55.7±6.0)、(38.3±6.7)vs(182.7±17.3)个,均P<0.05];同样浓度组的BGC-823穿膜细胞数目也显著降低[(88.7±8.3)、(49.0±5.7)、(42.3±6.7)vs(170.7±15.0)个,均P<0.05]。与对照组相比,DCA(60、80、100 mmol/L)组SGC-7901细胞的早期凋亡率显著增加[(31.7±5.2)%、(35.0±5.4)%、(37.8±6.2)%vs(8.1±1.3)%,均P<0.05)];BGC-823细胞的早期凋亡率也显著增加[(24.2±4.6)%、(31.9±4.2)%、(40.4±5.7)%vs(6.6±1.4)%,均P<0.05)]。结论:DCA明显抑制体外培养胃癌细胞的增殖,并可与化疗药物产生协同效应;DCA可抑制胃癌细胞的侵袭及诱导胃癌细胞凋亡;靶向丙酮酸脱氢酶激酶有望成为未来胃癌治疗新的方法。Objective： To explore the anti-tumor effect of dichloroacetate （ DCA）, an inhibitor of pyruvate dehydrogen- ase kinase, on gastric cancer cells in vitro. Methods： Gastric cancer cell SGC-7901 and BGC-823 lines cultured in vitro were treated respectively by different concentrations of DCA for 24 h. Viability rates of the gastric cancer cells were evalu- ated by MTT assay. The synergistic effect of DCA combined with cisplatin （DDP） on the gastric cancer cells was analyzed with the median effect principle. Invasive ability of the gastric cancer cells were then evaluated by Transwell assay. Their apoptotic rates were measured by double staining flow cytometry. Results： DCA （20, 40, 60, 80 and 100 mmolfL） re- markably reduced survival rates of the gastric cancer cells （SGC-7901and BGC-823 ） in a concentration-dependent man- ner. The ICs0 of DCA for 24 h in SGC-7901 and BGC-823 cells were 60.9 mmol/L and 53.8 mmol/L, respectively. Small-concentrations of DCA （20, 40 mmol/L） in combination with DDP （5, 10 μmol/L） synergistically reduced cell viability in the gastric cancer cells, their combination index was less than 1 both. Compared to control group, the number of invaded SGC-7901 cells in 60, 80 and 100 mmoL/L DCA groups significantly decreased （ [99.3 ± 11.7], [55.7 ± 6. 0 ] and [ 38.3 ± 6.7 ] vs [ 182.7 ± 17.3 ], P 〈 0.05 ] ; the number of invaded BGC-823 cells in the same concentra-tions of DCA groups also significantly decreased （ [ 88.7 ＋ 8.3 ], [49.0 ± 5.7 ] and [42.3 ± 6.7 ] vs [ 170.7 ± 15.0 ], P 〈0.05 ]. In addition, the early apoptotic rates of the SGC-7901 ceils in 60, 80 aad 100 mmoL/L DCA groups signifi- cantly increased （ [ 31.7 ± 5.2 ] %, [ 35.0 ± 5.4 ] %, [ 37.8 ± 6. 2 ] vs E 8.1 ±1.3 ] %, P 〈 0.05, compared to control group） ; while the early apoptotic rates of the BGC-823 cells in the same concentrations of DCA groups also significantly increased （ [24.6±4.61%, [31.9±4.21%, [40.4 ±5.71% vs [6.6±1.4]%, P〈0.05, compared to control group�

关 键 词：胃癌 二氯乙酸钠 顺铂 增殖 凋亡 侵袭 

分 类 号：R735.2[医药卫生—肿瘤] R730.54[医药卫生—临床医学]