龙葵碱通过调节miR-140和结肠癌转移相关基因1调控胃癌细胞增殖和凋亡  

Solanine regulates proliferation and apoptosis of gastric cancer cells by targeting miR-140/MACC1 pathway

作　　者：黄苗苗[1] 刘美英[1] 李保环 李坤[2] HUANG Miao-miao;LIU Mei-ying;LI Bao-huan;LI Kun(Department of Health Management,The Second Hospital of Shandong University,Jinan 250033,Shandong Province,China;Department of Gastroenterology,The First Affiliated Hospital of Shandong First Medical University,Qiartfoshan Hospital,Jinan 250000,Shandong Province,China)

机构地区：[1]山东大学第二医院健康管理科,山东济南250033 [2]山东第一医科大学附属第一医院、山东省千佛山医院消化内科,山东济南250000

出　　处：《中国临床药理学杂志》2020年第16期2440-2443,共4页The Chinese Journal of Clinical Pharmacology

基　　金：山东省科技发展计划基金资助项目(2014GSF118094)。

摘　　要：目的探讨龙葵碱对胃癌细胞增殖、凋亡的影响及其潜在分子机制。方法转染前,将胃癌SGC-7901细胞分为4组:对照组(常规培养)、低、中、高剂量龙葵碱组(分别给予25,50,100μg·mL-1龙葵碱处理48 h)。选用100μg·mL-1龙葵碱进行后续实验。将miRNA模拟物(miR-mimics)、miRNA抑制剂(miR-inhibitor)阴性对照及miR-140-mimics、miR-140-inhibitor分别转染至SGC-7901细胞,分别命名为第1转染组、第2转染组、第3转染组、第4转染组。将第3转染组和第4转染组细胞分别给予100μg·mL-1龙葵碱处理,分别命名为第5转染组和第6转染组。用噻唑蓝(MTT)法和流式细胞仪分别检测细胞增殖和凋亡情况,用实时荧光定量链式聚合酶反应(RT-qPCR)检测miR-140、结肠癌转移相关基因1(MACC1) mRNA相对表达量表达。结果对照组、高剂量龙葵碱组、第1转染组、第2转染组、第3转染组、第4转染组、第5转染组、第6转染组的细胞增殖率分别为(100.00±9.56)%,(45.88±6.22)%,(98.26±8.64)%,(64.27±5.73)%,(97.21±6.28)%,(152.87±11.05)%,(65.38±6.24)%,(93.24±7.68)%;细胞凋亡率分别为(4.68±0.56)%,(34.97±2.86)%,(4.46±0.54)%,(21.79±2.55)%,(5.31±0.58)%,(2.31±0.42)%,(21.56±2.42)%,(11.63±1.58)%;miR-140相对表达量分别为1.00±0.14,3.76±0.54,0.96±0.08,3.56±0.34,1.00±0.09,0.37±0.05,3.97±0.39,1.58±0.13;MACC1 mRNA相对表达量分别为1.00±0.08,0.44±0.06,0.97±0.07,0.47±0.05,0.99±0.08,2.16±0.17,0.56±0.06,0.92±0.07。以上指标,高剂量龙葵碱组与对照组比较,第2转染组和第1转染组比较,第4转染组和第3转染组比较,第6转染组和第5转染组比较,差异均有统计学意义(均P<0.05)。结论龙葵碱可能通过上调miR-140表达并下调MACC1表达,抑制胃癌SGC-7901细胞增殖并促进细胞凋亡。Objective To investigate the effect of solanine on proliferation and apoptosis of gastric cancer cells and its potential molecular mechanism. Methods Before transfection, SGC-7901 cells were divided into 4 groups: control group, low-dose solanine group, medium-dose solanine group, high-dose solanine group(treated with 25, 50, 100 μg·mL-1 solanine for 48 h, respectively). 100 μg·mL-1 solanine was used for further experiments. miR-mimics, miR-inhibitor negative control, miR-140-mimics and miR-140-inhibitor were transfected into SGC-7901 cells, respectively, and were named as miR-con group,miR-140 group,anti-miR-con group and anti-miR-140 group. Cells in the anti-miR-con group and the anti-miR-140 group were treated with high-dose solanine group,respectively,and were named as the solanine + anti-miR-con group and the solanine + anti-miR-140 group respectively. Cell proliferation and apoptosis were detected by MTT and flow cytometry. The miR-140 and colon cancer metastasis-related gene 1(MACC1) mRNA expression in cells were detected by RT-qPCR. Results The cell proliferation rates of the control group,the high-dose solaniline group,transfection-1 group,transfection-2 group,transfection-3 group,transfection-4 group, transfection-5 group and transfection-6 group were(100. 00 ± 9. 56) %,(45. 88 ± 6. 22) %,(98. 26 ± 8. 64) %,(64. 27 ± 5. 73) %,(97. 21 ± 6. 28) %,(152. 87 ± 11. 05) %,(65. 38 ± 6. 24) %,(93. 24 ± 7. 68) %,respectively;the apoptosis rates were(4. 68 ± 0. 56) %,(34. 97 ± 2. 86)%,(4. 46 ± 0. 54) %,(21. 79 ± 2. 55) %,(5. 31 ± 0. 58) %,(2. 31 ± 0. 42) %,(11. 63 ± 1. 58) %,respectively;the relative expressions of miR-140 were 1. 00 ± 0. 14,3. 76 ± 0. 54,0. 96 ± 0. 08,3. 56 ± 0. 34,1. 00 ± 0. 09,0. 37 ± 0. 05,3. 97 ± 0. 39,1. 58 ± 0. 13,respectively;the relative expression levels of MACC1 mRNA were 1. 00 ± 0. 08,0. 44 ± 0. 06,0. 97 ± 0. 07,0. 47 ± 0. 05,0. 99 ± 0. 08,2. 16 ± 0. 17,0. 56 ± 0. 06,0. 92 ± 0. 07,respectively. There were statistically significant differences between

关 键 词：胃癌 龙葵碱 miR-140 结肠癌转移相关基因1 增殖 凋亡 

分 类 号：R979.1[医药卫生—药品]