摘要
目的探讨左卡尼汀对氟尿嘧啶(5-fluorouracil,5-Fu)抑制人胃腺癌MGC803细胞增殖作用的影响。方法将MGC803细胞分为阴性对照组、5-Fu组、左卡尼汀和5-Fu联合用药组(左卡尼汀+/→5-Fu)进行实验。四甲基偶氮唑蓝(MTT)法检测细胞的增殖,流式细胞术检测细胞凋亡和细胞周期,蛋白质印迹法检测Bcl-2、Bax、ANT1和cleaved-PARP蛋白的表达。结果与5-Fu单药组相比,左卡尼汀和5-Fu联合用药组抑制MGC803细胞增殖的作用增强,细胞凋亡百分率增大,细胞周期S期阻滞,上调Bax、ANT1和cleaved-PARP蛋白的表达,下调Bcl-2蛋白的表达。实验结果还显示,左卡尼汀和5-Fu联合应用时,给药方法可以影响5-Fu对MGC803细胞的抑制作用。与左卡尼汀+5-Fu组相比,左卡尼汀→5-Fu组细胞凋亡百分率由(19.60±1.06)%增加至(24.17±3.12)%(P<0.05),G0/G1期细胞比例由(72.95±0.91)%降低至(62.62±1.04)%,S期细胞比例由(27.05±0.91)%增加至(37.35±1.03)%(P<0.001)。结论左卡尼汀可能通过影响Bcl-2家族蛋白的表达和细胞周期,增强5-Fu对MGC803细胞增殖的抑制作用。
OBJECTIVE To investigate the efiects of combination treatment with L-carnitine and 5-fluorouraeil on the proliferation and cell apoptosis of gastric cancer MGC803 cells. METHODS MGCS03 cells were divided into control group, 5-fluorouracil group and the combination of L-carnitine and 5-fluorouraeil group （L-carnitine ＋/→5-flaorouraeil group） in vitro, The inhibitory rate of cells was measured by MTT assay. The apoptosis rate and cell cycle of cells were detected by FLOW. Western blot was used to analyzed the expression of Bel-2, Bax, adenine nucleotide trans｜ocatorl （ ANT1 ） and eleaved-PARP. RESULTS Compared with 5-fluorouraeil group, the inhibition rate of MGC803 cells was increased when cells were treated with the combination of L-carnitine and 5-fluorouracil. The apoptosis rate of cells was raised and the cells were blocked at S phase. In addition, the combination group can decrease the ex- pression of Bel-2 and increase the expression of Bax, ANT1 and cleaved-PARP. At the same time, the apoptosis rate of ceils and the cell cycle were different with the different dosage regimen when treated with the combination. Compared with the L-carnitine ＋ 5-flu- orouraeil group, the apoptosis rate of cells was increased to （24. 17 ±3. 12 ） % from （ 19. 60± 1.06） % （ P 〈 O. 05 ）. The G0/G1 phase proportion of cells was decreased to （62. 62± 1.04） % from （72.95 ± 0. 91 ） % ,and the S phase proportion of cells was increased to （37.35 ±1.03）% from （27.05 ±0.91）% （P〈0.001）. CONCLUSION Treatment with L-carnitine and 5-fluorouracil could en- hance the inhibitory effect of 5-fluorouraeil on MGC803 ceils. The possible mechanism of action is achieved by regulating the expression of Bel-2 protein family and influencing the cell cycle.
作者
郎娟娟
钱兴运
陶若琳
刘艳霞
王晨
LANG Juan-juan QIAN Xing-yun TAO Ruo-lin LIU Yan-xia WANG Chen(Department of Pharmacy, Tianjin Medical University Cancer Institute and Hospital ,National Clinical Research Center for Cancer, Key Laboratory of Tianjin Cancer Preven- tion and Therapy, Tianjin＇s Clinical Research Center for Cancer, Tianjin 30060, China Department of Pharmacology, School of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2016年第24期2102-2108,共7页
Chinese Pharmaceutical Journal
基金
天津市应用基础与前沿技术研究计划(一般项目)(14JCYBJC28600)
