MK801对结肠癌细胞增殖、凋亡和迁移的影响  

Effects of MK801 on proliferation,apoptosis and migration of colorectal cancer cells

作　　者：谢冬冰[1] 孟建宇[2] 郭玉婷[3] 任霞[4] 李雪[1] 

机构地区：[1]山东中医药大学第二临床学院,250014 [2]山东中医药大学理工学院 [3]山东中医药大学附属第二医院消化科 [4]山东省医学科学院基础所

出　　处：《天津医药》2016年第11期1334-1337,1409,共5页Tianjin Medical Journal

基　　金：山东省自然科学基金资助项目(Y2008C141)

摘　　要：目的探究N-甲基-D-天冬氨酸受体亚型1(NMDAR1)在结肠癌细胞HT29和SW116中的表达,以及NMDAR1拮抗剂MK801对HT-29和SW116细胞生长抑制、凋亡和迁移的影响。方法采用免疫组织化学法检测结肠癌细胞HT-29和SW116细胞表面NMDAR1的表达;应用噻唑蓝(MTT)比色法测定62.5、125.0、250.0、500.0、1 000.0、2 000.0μmol/L的MK801对于HT-29和SW116细胞增殖作用的影响;应用流式细胞术检测2 000μmol/L的MK801对HT29和SW116细胞凋亡的影响;应用细胞划痕实验检测50μmol/L MK801对于结肠癌细胞HT-29和SW116迁移能力的影响。结果结肠癌细胞HT-29和SW116均表达NMDAR1,且主要表达于细胞质中;各浓度的MK801对HT-29细胞,以及浓度为500.0、1 000.0、2 000.0μmol/L的MK801对SW116细胞的生长抑制作用具有时间效应关系,24、48及72 h各MK801浓度组对HT-29和SW116细胞的抑制率随浓度升高整体呈增强趋势,但抑制率不呈明显的剂量效应关系;MK801具有促进HT-29和SW116细胞凋亡的作用,且主要表现诱导细胞早期凋亡;MK801可抑制HT-29和SW116细胞迁移。结论 NMDAR1在结肠癌细胞胞质中表达,且NMDAR1拮抗剂MK801具有抑制肿瘤细胞生长、迁移,促进其早期凋亡的作用,有望成为新一代抗肿瘤药物。Objective To explore the expression of the N- methyl- D- aspartate receptor type 1(NMDAR1) in thecolorectal cancer cells(CRC), and to examine the effects of NMDAR1 antagonists MK801 on proliferation, apoptosis andmigration of colorectal cancer cell line HT-29 and SW116 cells. Methods The immunocytochemistry method was used toexamine the expressions of NMDAR1 in HT-29 and SW116 cells. MTT assay was used to detect the effects of MK801(62.5,125.0, 250.0, 500.0, 1 000.0, 2 000.0 μmol/L) on the proliferation of HT-29 and SW116 cells. The flow cytometry was usedto analyze the effect of MK801(2 000 μmol/L) on cell apoptosis of HT-29 and SW116 cells. Wound healing assay was usedto detect the effect of MK801(50 μmol/L) on the migration of HT- 29 or SW116 cells. Results The NMDAR1 wasexpressed in both HT- 29 and SW116 cells, and mainly in the cytoplasm. MTT assay showed that there were inhibitoryeffects of different concentrations of MK 801(62.5, 125.0, 250.0, 500.0, 1 000.0, 2 000.0 μmol/L) on the proliferation of HT-29 cells, and inhibitory effects of different concentrations of MK801(500.0, 1 000.0, 2 000.0 μmol/L) on SW116 cells, in atime- dependent manner. For 24, 48 and 72 h, the inhibitory effects of MK801 on proliferation rates of HT-29 and SW116 cells were increased with the increased concentrations of MK801. MK801 showed an effect to induce cell apoptosis in HT-29 and SW116 cells, and mainly for early apoptosis. Wound healing assay indicated that MK801 inhibited the cell migrationof HT-29 and SW116 cells. Conclusion Results suggest that there is expression of NMDAR1 in colorectal cancer cells.The NMDAR1 antagonist MK801 can inhibit the proliferation, induce cells early apoptosis and inhibit cells migration. It maybe a new generation of antitumor drugs.

关 键 词：结肠肿瘤 细胞增殖 细胞凋亡 细胞运动 体外研究 N-甲基-D-天冬氨酸受体亚型1 MK801 HT-29 SW116 

分 类 号：R735.35[医药卫生—肿瘤]