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。
Abstract
OBJECTIVE To investigate the effects of combination treatment with L-carnitine and 5-fluorouracil on the proliferation and cell apoptosis of gastric cancer MGC803 cells. METHODS MGC803 cells were divided into control group, 5-fluorouracil group and the combination of L-carnitine and 5-fluorouracil group (L-carnitine+/→5-fluorouracil 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 Bcl-2, Bax, adenine nucleotide translocator1(ANT1) and cleaved-PARP. RESULTS Compared with 5-fluorouracil 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 expression of Bcl-2 and increase the expression of Bax, ANT1 and cleaved-PARP. At the same time, the apoptosis rate of cells and the cell cycle were different with the different dosage regimen when treated with the combination. Compared with the L-carnitine+5-fluorouracil group, the apoptosis rate of cells was increased to (24.17±3.12)% from (19.60±1.06)% (P<0.05). 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 enhance the inhibitory effect of 5-fluorouracil on MGC803 cells. The possible mechanism of action is achieved by regulating the expression of Bcl-2 protein family and influencing the cell cycle.
关键词
MGC803细胞 /
左卡尼汀 /
氟尿嘧啶 /
联合应用 /
给药方法 /
细胞凋亡
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Key words
MGC803 cells /
L-carnitine /
5-fluorouracil /
combination treatment /
dosage regimen /
cell apoptosis
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中图分类号：
R965
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参考文献
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脚注
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基金
天津市应用基础与前沿技术研究计划(一般项目)(14JCYBJC28600)
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