联苯呋喃香豆素类衍生物BFD-6b抗结肠癌作用的初步研究  

The anti-colorectal cancer effect of biphenyl-furocoumarin derivative BFD-6b

作　　者：李军 田秋梅 闫蓉[2] 郭敏 吴方雄 LI Jun;TIAN Qiumei;YAN Rong;GUO Min;WU Fangxiong(Tumor Department No.2 Sengong Hospital of Shaanxi Province,Xi’an 710300;Department of Gastroenterology,The First Affiliated Hospital of Xi’an Medical University,Xi’an 710077,China)

机构地区：[1]陕西省森林工业职工医院肿瘤二科,陕西西安710300 [2]西安医学院第一附属医院消化内科,陕西西安710077

出　　处：《西安交通大学学报（医学版）》2022年第4期612-618,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：陕西省教育厅专项科研计划项目(No.2012JK0704)。

摘　　要：目的研究BFD-6b对结肠癌细胞的增殖抑制作用及其初步机制。方法使用MTT法检测BFD-6b对多种肿瘤细胞SW480、MCF-7、T47D、SMMC-7721、BEL-7402、97H、SK-HEP-1、H460、H1299、A549、MS751、HELA等的增殖抑制作用,筛选出对BFD-6b最敏感的细胞株;采用流式细胞术检测BFD-6b对细胞凋亡及细胞周期的影响;蛋白免疫印迹法检测BFD-6b对周期相关蛋白和凋亡相关蛋白表达的影响。结果BFD-6b对不同肿瘤细胞SW480、MCF-7、H460、H1299、A549、HELA等的增殖均有一定的抑制效果,其中对结肠癌细胞SW480抑制作用最明显且呈浓度依赖性,其IC_(50)值为7.09μmol/L;同时,BFD-6b对SW620、Lovo、HCT116结肠癌细胞增殖均有较强的抑制作用,且呈浓度依赖性,其IC_(50)值分别为7.23、8.08、8.96μmol/L。进一步研究发现,BFD-6b对SW480细胞增殖具有浓度及时间依赖关系,其作用时间为24、48、72 h的IC_(50)值分别为>50、7.09及5.86μmol/L。BFD-6b通过下调CyclinD1、CyclinE以及细胞周期依赖性激酶CDC2蛋白表达量,从而阻滞细胞周期于G1期;通过下调抑凋亡蛋白Mcl-1、Bcl-2表达量,上调促凋亡蛋白BAK、BAX表达量,从而诱导SW480细胞凋亡,进一步抑制细胞生长。结论BFD-6b通过下调CyclinD1、CyclinE以及细胞周期依赖性激酶CDC2蛋白表达,阻滞SW480细胞于G1期;通过下调抑凋亡蛋白Mcl-1、Bcl-2表达,上调促凋亡蛋白BAK、BAX表达诱导细胞凋亡,从而抑制结肠癌细胞SW480的增殖。Objective To investigate the inhibitory effect of BFD-6b on colorectal cancer cell growth and its preliminary mechanism.Methods The inhibitory effect of BFD-6b on the growth of various tumor cells(SW480,MCF-7,T47D,SMMC-7721,BEL-7402,97H,SK-HEP-1,H460,H1299,A549,MS751,and HELA)was investigated by MTT assay;the effect of BFD-6b on apoptosis and cell cycle was detected by flow cytometry;the effect of BFD-6b on the expressions of cell cycle-related proteins and apoptosis-related proteins was examined by Western blotting.Results BFD-6b inhibited the proliferation of different cancer cells such as SW480,MCF-7,H460,H1299,A549,and HELA.Among all of them,SW480 cells were most sensitive to BFD-6b,and the IC_(50)value was 7.09μmol/L.Furthermore,BFD-6b could inhibit the growth of another three colorectal cell(SW620,Lovo,and HCT116 cells);the IC_(50)values were 7.23,8.08 and 8.96μmol/L,respectively.BFD-6b could downregulate the amount of cyclinD1,cyclinE,and cell cycledependent kinase CDC2,thereby arresting the cell cycle at G1phase.Also,BFD-6b downregulated the expressions of antiapoptotic proteins Mcl-1 and Bcl-2,and upregulated the expressions of pro-apoptotic proteins BAK and BAX,thus inducing apoptosis of SW480 cells.Conclusion BFD-6b arrests SW480 cells at G1phase by downregulating the expressions of cyclinD1,cyclinE and CDC2,and induces SW480 cell apoptosis by downregulating the expressions of Mcl-1and Bcl-2 and upregulating the expressions of BAK and BAX,thereby inhibiting the proliferation of colorectal cancer SW480 cells.

关 键 词：BFD-6b 结肠癌 SW480 细胞凋亡 细胞周期 

分 类 号：R285.5[医药卫生—中药学]