新型硫色满酮衍生物的体外抗肿瘤活性及作用机制  

In vitro anticancer effects and possible mechanism of new synthesized thiochromanone derivatives

作　　者：苏立敏[1] 刘玉欣[1,2] 黄鑫[1] 何洋[1] 王士奎[1] 马正月[1] 杨更亮[1,2] 

机构地区：[1]河北大学药学院 [2]河北大学河北省药物质量分析控制重点实验室,保定071002

出　　处：《中国新药杂志》2012年第6期675-680,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金(20375010);河北大学研究基金(y2008118);河北省高等学校科学技术研究重点项目(ZD2010234);河北省应用基础研究计划重点基础研究项目(11966411D)

摘　　要：目的:观察(顺)-3(氯代亚甲基)-5,7-二甲基-硫色满-4-酮[(Z)-3(chloromethylene)-5,7(dim-ethyl)-thiochroman-4-ketone,CMDMT]以及(顺)-3(氯代亚甲基)-5,7-二氯-硫色满-4-酮[(Z)-3(chloromethyl-ene)-5,7(dichloro)-thiochroman-4-ketone,CMDCT]对6种肿瘤细胞生长的抑制作用;初步探讨CMDMT诱导HepG-2细胞凋亡的机制。方法:采用MTT法检测不同浓度的CMDMT及CMDCT对体外培养的5种人源肿瘤细胞(U937,K562,A375,786O和HepG-2)以及1种鼠源肿瘤细胞(S180)的生长抑制作用;台盼蓝染色细胞计数法测定CMDMT作用后HepG-2细胞存活率,绘制细胞生长曲线;TUNEL法形态学观察CMDMT对HepG-2细胞凋亡的影响;流式细胞术(FCM)检测HepG-2细胞的凋亡率;ELISA法检测细胞内半胱氨酸蛋白酶3(caspase-3)的含量。结果:CMDMT和CMDCT对6种肿瘤细胞系的生长呈浓度依赖性抑制作用;化合物CMDMT的半数抑制浓度在8.34～17.57μmol.L-1之间,CMDCT在10.73～24.29μmol.L-1之间。TUNEL法和流式细胞术结果表明CMDMT以浓度依赖方式诱导HepG-2细胞凋亡。CMDMT能明显增加caspase-3的含量。结论:CMDMT和CMDCT具有较广泛的体外抗肿瘤活性,CMDMT具有诱导HepG-2细胞凋亡的作用,二者可作为抗肿瘤药物的先导化合物。Objective： To determine the in vitro inhibitory effects of （Z）-3 （chloromethylene）-5,7 （dime- thyl） -thiochroman-4-ketone （CMDMT） and （Z） -3 （ chloromethylene ）-5,7 （ dichloro ）-thiochroman-4-ketone （CMDCT） on 6 tumor cell lines, and to explore the anti-apoptotic mechanism of CMDMT in the human liver cancer cell line HepG-2 cells. Methods： MTT assay was used to test the inhibitory effect of CMDMT and CMDCT on 5 hu- man cancer cell lines （U937, K562, A375, 7860, HepG-2 cells） and a murine cancer cell line （S180 cells）. The trypan blue exclusion method was used to count the number of viable and dead cells for drawing cell growth curve. The apoptotic cell was detected by TUNEL assay. Apoptosis of the human liver cancer cell line HepG-2 ceils was measured by Annexin V/PI dual-color flow cytometry （FCM）. The amount of caspase-3 in HepG-2 cells was measured by ELISA method. Results： The growth of the 6 tumor cell lines was restrained by CMDMT or CMDCT in a concentration-dependent manner. The 50% inhibiting concentrations （IC50） of CMDMT and CMDCT on 6 cancer cell lines were 8.34 -17.57 μmol.L^-1 and 10.73 -24.29 μmol. L^-1. TUNEL assay and FCM results showed that CMDMT induced apoptosis of HepG-2 cells in a concentration-dependent manner; CMDMT increased the amount of caspase-3 in HepG-2 cells. Conclusion： CMDMT and CMDCT show a dramatic in vitro anti-tumor activity and CMD- MT can induce HepG-2 cell apoptosis, suggesting that two chemicals may be potential anticancer lead compounds.

关 键 词：(顺)-3(氯代亚甲基)-5 7-二甲基-硫色满-4-酮(CMDMT) (顺)-3(氯代亚甲基)-5 7-二氯-硫色满-4-酮(CMDCT) MTT法 抗肿瘤活性 半数抑制浓度 细胞凋亡 

分 类 号：R979.1[医药卫生—药品]